influenza virus characterisation, june 2017 · 2017. 8. 22. · influenza virus isolates,...
TRANSCRIPT
This report was prepared by Rod Daniels, Vicki Gregory, Burcu Ermetal, Aine Rattigan and John McCauley for the European
Centre for Disease Prevention and Control (ECDC) under an ECDC framework contract.
Suggested citation: European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, June
2017. Stockholm: ECDC; 2017.
© European Centre for Disease Prevention and Control, Stockholm, 2017.
Reproduction is authorised, provided the source is acknowledged.
Summary In the course of the 2016–2017 influenza season, nearly 146 000 influenza detections across the EU/EAA region have been reported. Influenza type A viruses have prevailed over type B with A(H3N2) viruses, greatly outnumbering A(H1N1)pdm09 and B/Yamagata-lineage detections representing 73% of the type B viruses assigned to a lineage.
Since 1 January 2017 EU/EEA countries have shared 1039 influenza-positive specimens with the WHO Collaborating Centre (CC), London, for detailed characterisation: 518 of these had collection dates after 31 December 2016. Subsequent to the WHO CC’s Vaccine Composition Meeting (VCM) report for February 2017, 217 viruses were characterised antigenically and 525 genetically, many with collection dates prior to 1 January 2017. Many A(H3N2) viruses could only be characterised genetically as HA titres were too low to allow antigenic characterisation by haemagglutination inhibition assay. Post-VCM report results are presented and discussed in this ECDC virus characterisation report.
All 22 A(H1N1)pdm09 viruses characterised antigenically were similar to the 2016–17 vaccine virus, A/California/7/2009, but showed somewhat better reactivity with antiserum raised against the subclade 6B.1 2017–18 vaccine virus, A/Michigan/45/2015. Subclade 6B.1 viruses, defined by HA1 amino acid substitutions S162N and I216T, became dominant worldwide and all 16 EU/EEA viruses characterised with 2017 collection dates, were within this subclade.
The 105 A(H3N2) test viruses able to be characterised by haemagglutination inhibition (HI) assay were recognised well by antisera raised against egg-propagated A/Hong Kong/4801/2014 (the current vaccine component) and several cell culture-propagated viruses in the 3C.2a clade. Of 147 A(H3N2) viruses characterised genetically with collection dates in 2017, 38 (26%) were subclade 3C.2a, 108 (73%) were subclade 3C.2a1, and 1 (1%) was subclade 3C.3a.
Of the 32 B/Victoria-lineage viruses tested, 31 were antigenically similar to tissue culture-propagated surrogates of B/Brisbane/60/2008. One virus, B/Norway/2409/2017, gave no reactivity with any of the ferret antisera used and was shown to have a deletion of two amino acids in HA1 at positions 162 and 163. All 23 viruses characterised with collection dates in 2017, including the viruses with the deletion in the HA, fell in genetic clade 1A, as do recently collected viruses worldwide.
Of the 58 B/Yamagata viruses characterised antigenically, 42 reacted well with post-infection ferret antiserum raised against egg-propagated B/Phuket/3073/2013, the recommended vaccine virus for the northern hemisphere 2015–16 influenza season and for quadrivalent vaccines since 2016. Of the 44 viruses characterised with 2017 collection dates, all fell in genetic clade 3.
Influenza virus
characterisation Summary Europe, July 2012
Influenzavirus characterisation
Summary Europe, June 2017
SURVEILLANCE REPORT
Influenza virus characterisation
Summary Europe, June 2017
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
2
Table 1 shows a summary of influenza virus detections in the WHO European Region reported to TESSy for the weekly reporting period (weeks 40/2016–20/2017) of the 2016–17 season. Approximately 146 000 detections had
been made with type A viruses prevailing over type B at a ratio of 6.8:1. As of week 20/2016, of the type A viruses subtyped (n = 53 511) and the type B viruses ascribed to lineage (n = 2 571), A(H3N2) had prevailed over A(H1N1)pdm09 and B/Yamagata over B/Victoria by ratios of 99.0:1 and 2.5:1, respectively. While relatively few influenza detections have been reported for weeks 21–29/2017, it is notable that the ratios for type A:type B and A(H3N2):A(H1N1)pdm09 have dropped to 0.2:1 and 3.8:1, respectively, while the B/Yamagata:B/Victoria ratio has increased to 10.6:1.
Since 1 January 2017, 50 shipments of specimens have been received at the Crick Worldwide Influenza Centre (WIC), from countries in the EU/EEA. These packages contained 518 specimens, a mix of clinical samples and virus isolates originating from 21 countries in EU/EAA, with collection dates after 31 December 2016 (Table 2). The majority (73%) were type A viruses, and A(H3N2) outnumbered A(H1N1)pdm09 at a ratio of 10.5:1. Of the 137 type B specimens received (26% of the specimens), 52 were B/Victoria-lineage and 82 were B/Yamagata-lineage. Many specimens are still in the process of being characterised. The antigenic and genetic properties of influenza virus isolates, characterised since the February 2017 Crick Worldwide Influenza Centre Vaccine
Composition Meeting (VCM) report1, are presented and discussed in this surveillance report.
Table 1. Influenza virus detections in the WHO European Region from the start of reporting for the 2016–17 season (week 40/2016)
_____
1 Worldwide Influenza Centre at the Francis Crick Institute, a WHO Collaborating Centre for Reference and Research on Influenza. Report prepared for the WHO annual consultation on the composition of influenza vaccines for use in the northern hemisphere 2017–2018 [14].
Virus type/subtype/lineage
Weeks
40/2016-20/2017
Weeks
21-29/2017
Weeks
40/2016-20/2017
Weeks
21-29/2017
Weeks
40/2016-20/2017
Weeks
21-29/2017
Weeks
40/2016-20/2017
Weeks
21-29/2017
Weeks
40/2016-20/2017
Weeks
21-29/2017
Influenza A 16 240 11 110 018 186 126 258 197 87.2 16.6 6.8:1 0.2:1
A(H1N1)pdm09 187 6 370 13 557 19 1.0 20.7
A(H3N2) 13 574 3 39 380 70 52 954 73 99.0 79.3 99.0:1 3.8:1
A not subtyped 2 479 2 70 268 103 72 747 105
Influenza B 1 961 23 16 557 965 18 518 988 12.8 83.4
Victoria lineage 386 5 346 11 732 16 28.5 8.6
Yamagata lineage 481 1 1 358 169 1 839 170 71.5 91.4 2.5:1 10.6:1
Lineage not ascribed 1 094 17 14 853 785 15 947 802
Total detections (total tested) 18 201 (50 975) 34 (1 079) 126 575 (589 447) 1 151 (26 936) 144 776 (640 422) 1 185 (28 015)
Cumulative number of detections
* Percentages are shown for total detections (types A & B [in bold type], and for viruses ascribed to influenza A subtype and influenza B lineage). Ratios are given for type A:B [in bold type], A(H3N2):A(H1N1)pdm09
and Yamagata:Victoria lineages.
Sentinel sources Non-sentinel sources Totals
Totals*
Ratios%
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
3
Table 2. Summary of clinical samples and virus isolates, with collection dates after 31 December 2016, received from EU/EEA Member States
MONTH* TOTAL
RECEIVED
Country
2017
JANUARY
Austria 1 1 in process
Belgium 20 20 2 16
Bulgaria 39 4 in process 35 in process
Cyprus 18 18 in process
Germany 33 5 5 22 in process 1 1 5 5
Greece 36 27 8 16 1 0 8 4
Ireland 3 1 1 2 1 1
Italy 7 6 in process 1 in process
Latvia 5 4 1 2 1 1
Luxembourg 2 2 0 2
Norway 7 2 2 3 in process 2 in process
Poland 28 1 in process 27 in process
Portugal 1 1 1
Romania 15 15 0 15
Slovakia 15 13 in process 1 in process 1 in process
Slovenia 18 10 in process 8 in process
Spain 6 5 in process 1 1
2017
FEBRUARY
Austria 16 3 in process 7 in process 6 in process
Belgium 9 7 in process 1 in process 1 in process
Bulgaria 12 2 2 7 1 6 3 2
France 2 2 in process
Germany 15 5 in process 4 in process 2 2 4 4
Greece 7 1 0 5 0 0 1 0
Iceland 13 10 7 3 3 3
Italy 9 2 1 7 in process
Latvia 9 5 3 2 1 1 3 3
Lithuania 5 4 3 1 1 1
Norway 31 2 1 14 2 12 8 5 7 5
Poland 10 10 0 5
Slovakia 9 2 2 3 in process 3 3 1 1
Slovenia 7 5 in process 2 2
Spain 1 1 1 0
Sweden 4 3 in process 1 in process
2017
MARCH
Austria 3 1 in process 1 in process 1 in process
Bulgaria 1 1 0 1
Germany 13 8 in process 3 in process 2 2
Iceland 6 4 2 2 2 2
Italy 3 3 2
Latvia 2 1 0 1 1 1
Lithuania 6 1 1 0 1 1 4 4
Norway 17 1 1 11 in process 1 0 4 3
Poland 6 6 0 2
Slovakia 1 1 1
Slovenia 7 2 in process 1 1 4 4
2017
APRIL
Austria 2 2 in process
Germany 4 2 in process 1 1 1 1
Latvia 2 1 1 0 1 1
Norway 24 3 3 4 1 3 9 in process 8 8
Poland 1 1 0
Slovakia 1 1 1
Slovenia 1 1 1
2017
MAY
Norway 5 3 1 1 2 2
518 1 0 33 18 347 35 91 3 0 52 24 82 57
21 Countries
* Month indicates the months in which the clinical specimens were collected
1. Propagated to sufficient titre to perform HI assay
2. Propagated to sufficient titre to perform HI assay in presence of 20nM oseltamivir; numbers in red indicate viruses recovered but with insufficient HA titre to permit HI assay
B Yamagata lineageH1N1pdm09 H3N2 B B Victoria lineage
10.0% 15.8%
73.4% 26.4%
Number
propagated1
Number
received
Number
propagated1
Number
received
Number
propagated2
Number
received
Number
propagated
Number
received
Number
propagated1
Number
received
A
Number
received
Number
propagated
0.2% 0.6%6.4% 67.0%
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
4
Influenza A(H1N1)pdm09 virus analyses Results of haemagglutination inhibition (HI) analyses of viruses performed since the February 2017 VCM report [14] are shown in Table 3. All 22 A(H1N1)pdm09 viruses from EU/EEA countries antigenically characterised were similar to the vaccine virus for the forthcoming northern hemisphere 2017–18 influenza season, A/Michigan/45/2015, with all viruses being recognised at titres within twofold of the homologous titre of the antiserum. The antiserum raised against A/California/7/2009, the vaccine virus recommended for use for the northern hemisphere 2016–17 influenza season, recognised all but two of the test viruses gave titres at within twofold of the titre of the antiserum for the homologous virus. Generally, test viruses were recognised by the panel of antisera at titres within fourfold of the titres of the antisera with their respective homologous viruses.
Exceptions were observed with antisera raised against A/Lviv/N6/2009, A/St. Petersburg/100/2011 and A/Israel/Q-504/2015. These antisera recognised 4/22 (18%), 9/22 (41%) and 18/22 (82%) test viruses at titres within fourfold of titres for the homologous viruses, respectively. Reference viruses carrying HA1 G155E amino acid substitutions, A/Bayern/69/2009 and A/Lviv/N6/2009, showed reduced recognition (fourfold or greater) by the
antisera raised against both vaccine viruses and reference viruses in genetic clades 5, 6, 7, 6B, 6B.1 and 6B.2.
All test viruses sequenced after the report for the February 2017 WHO VCM belong to genetic subclade 6B.1 (Table 1 and Figure 1). Since 2009, the HA genes have evolved, and nine clades have been designated. For approximately three years, viruses in clade 6 represented by A/St Petersburg/27/2011 and carrying amino acid substitutions of D97N, S185T and S203T in HA1 and E47K and S124N in HA2, compared with A/California/7/2009, have predominated worldwide with a number of subgroups emerging. All EU/EEA viruses characterised since the September 2014 report2 carry HA genes in subgroup 6B, which is characterised by additional amino acid substitutions of K163Q, A256T and K283E in HA1 and E172K in HA2 compared with A/California/7/2009, e.g. A/South Africa/3626/2013. A number of virus clusters have emerged within subgroup 6B, and two of these have been designated as subclades. Viruses in subclade 6B.1, represented by A/Michigan/45/2015, are defined by HA1 amino acid substitutions S84N, S162N (which results in the formation of a new potential glycosylation motif at residues 162-164 of HA1) and I216T. Those in subclade 6B.2 are defined by HA1 amino acid substitutions V152T and V173I, represented by A/Israel/Q-504/2015. All viruses examined fell into subclade 6B.1.
During the 2016–2017 influenza season, A(H1N1)pdm09 activity has been low compared to the previous season, and the viruses involved remained antigenically indistinguishable by post-infection ferret antisera raised against the A/California/7/2009 vaccine virus. The basis for the change of the A(H1N1)pdm09 component in the vaccine was described in the September 2016 ECDC characterisation report3. To summarise, studies with post-vaccination and post-infection human sera showed that a significant proportion could distinguish representative viruses of subclades 6B.1 and 6B.2 from the vaccine virus. Moreover, the reports of high levels of infection associated with A(H1N1)pdm09 in many countries, and the great dominance of subclade 6B.1 viruses among the H1N1pdm09 viruses in circulation led to the recommendation made by WHO to include an A/Michigan/45/2015–like virus in vaccines for the 2017 southern hemisphere and 2017–18 northern hemisphere influenza seasons [1,2].
_____
2 European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, September 2014.
Stockholm: ECDC; 2014. Available from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/Influenza-ERLI-Net-report-Sept-2014.pdf
3 European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, September 2016.
Stockholm: ECDC; 2016. Available from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/influenza-virus-characterisation-september-2016.pdf
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
5
Table 3. Antigenic analysis of A(H1N1)pdm09 viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
e
A/M
ich
A/C
al
A/B
aye
rnA
/Lv
ivA
/As
tra
kA
/St.
PA
/St.
PA
/HK
A/S
th A
frA
/Slo
vA
/Is
rae
l
info
rma
tio
nd
ate
h
isto
ry4
5/1
57
/09
69
/09
N6
/09
1/1
12
7/1
11
00
/11
56
59
/12
36
26
/13
29
03
/20
15
Q-5
04
/15
Pa
ss
ag
e h
isto
ryE
gg
Eg
gM
DC
KM
DC
KM
DC
KE
gg
Eg
gM
DC
KE
gg
Eg
gM
DC
K
Fe
rre
t n
um
be
rN
IB F
42
/16
*1F
06
/16
*1F
09
/15
*1F
14
/13
*1F
22
/13
*1F
26
/14
*1F
24
/11
*1F
30
/12
*1F
03
/14
*1F
02
/16
*2F
08
/16
*2
Ge
ne
tic
gro
up
6B
.15
67
6A
6B
6B
.16
B.2
RE
FE
RE
NC
E V
IRU
SE
S
A/M
ich
iga
n/4
5/2
01
56
B.1
20
15
-09
-07
E3
/E2
64
06
40
32
01
60
64
03
20
12
80
12
80
64
01
28
06
40
A/C
alifo
rnia
/7/2
00
9c
lon
e 3
8-3
22
00
9-0
4-0
9E
3/E
46
40
64
03
20
16
06
40
32
01
28
06
40
64
01
28
06
40
A/B
aye
rn/6
9/2
00
92
00
9-0
7-0
1M
DC
K5
/MD
CK
14
04
03
20
16
08
04
04
08
08
08
04
0G
15
5E
A/L
viv
/N6
/20
09
20
09
-10
-27
MD
CK
4/S
IAT
1/M
DC
K3
16
01
60
12
80
12
80
80
80
16
03
20
80
16
01
60
G1
55
E>
G,
D2
22
G
A/A
str
ak
ha
n/1
/20
11
52
01
1-0
2-2
8M
DC
K1
/MD
CK
52
56
01
28
01
28
06
40
12
80
64
02
56
02
56
01
28
02
56
01
28
0
A/S
t. P
ete
rsb
urg
/27
/20
11
62
01
1-0
2-1
4E
1/E
42
56
01
28
01
28
06
40
25
60
64
02
56
02
56
01
28
02
56
01
28
0
A/S
t. P
ete
rsb
urg
/10
0/2
01
17
20
11
-03
-14
E1
/E4
51
20
51
20
25
60
12
80
51
20
12
80
51
20
51
20
51
20
51
20
51
20
A/H
on
g K
on
g/5
65
9/2
01
26
A2
01
2-0
5-2
1M
DC
K4
/MD
CK
23
20
16
01
60
80
16
03
20
32
06
40
16
03
20
32
0
A/S
ou
th A
fric
a/3
62
6/2
01
36
B2
01
3-0
6-0
6E
1/E
31
28
06
40
64
06
40
64
06
40
12
80
12
80
12
80
12
80
64
0
A/S
lov
en
ia/2
90
3/2
01
5c
lon
e 3
76
B.1
20
15
-10
-26
E4
/E1
25
60
25
60
64
06
40
12
80
64
02
56
02
56
01
28
02
56
02
56
0
A/Is
rae
l/Q
-50
4/2
01
56
B.2
20
15
-12
-15
C1
/MD
CK
22
56
01
28
06
40
32
01
28
06
40
25
60
25
60
12
80
25
60
25
60
TE
ST
VIR
US
ES
A/S
as
sa
ri/1
/20
16
6B
.12
01
6-1
2-3
0M
DC
K3
/MD
CK
16
40
64
03
20
16
06
40
32
01
28
01
28
06
40
25
60
12
80
A/B
ulg
ari
a/5
8/2
01
76
B.1
20
17
-01
-02
SIA
T2
/MD
CK
16
40
32
01
60
80
32
01
60
64
03
20
32
06
40
32
0
A/B
ulg
ari
a/2
6/2
01
76
B.1
20
17
-01
-02
SIA
T2
/MD
CK
16
40
32
01
60
80
32
01
60
64
06
40
32
06
40
64
0
A/B
ulg
ari
a/3
12
/20
17
6B
.12
01
7-0
1-1
1S
IAT
2/M
DC
K1
64
03
20
16
08
03
20
16
06
40
64
03
20
64
03
20
A/S
ac
hs
en
/26
/20
17
6B
.12
01
7-0
1-2
6C
2/M
DC
K1
64
03
20
16
08
03
20
32
06
40
64
06
40
12
80
64
0
A/N
orw
ay/7
86
/20
17
6B
.12
01
7-0
1-2
7M
DC
K1
/MD
CK
16
40
32
01
60
16
06
40
16
06
40
64
06
40
12
80
64
0
A/N
orw
ay/8
07
/20
17
6B
.12
01
7-0
1-2
7M
DC
K1
/MD
CK
16
40
32
01
60
80
32
01
60
64
06
40
64
01
28
03
20
A/S
ac
hs
en
-An
ha
lt/3
/20
17
6B
.12
01
7-0
1-2
7C
1/M
DC
K1
32
03
20
80
40
32
01
60
64
06
40
32
06
40
64
0
A/S
ac
hs
en
/41
/20
17
6B
.12
01
7-0
1-2
7C
1/M
DC
K1
12
80
16
03
20
32
03
20
16
06
40
32
03
20
64
06
40
A/N
ied
ers
ac
hs
en
/10
1/2
01
76
B.1
20
17
-02
-01
C1
/MD
CK
13
20
32
01
60
80
32
01
60
64
03
20
32
06
40
32
0
A/B
ulg
ari
a/4
30
/20
17
6B
.12
01
7-0
2-0
1S
IAT
2/M
DC
K1
64
03
20
16
01
60
32
01
60
64
06
40
32
01
28
06
40
A/B
ulg
ari
a/4
29
/20
17
6B
.12
01
7-0
2-0
1S
IAT
2/M
DC
K1
64
03
20
32
01
60
32
01
60
12
80
64
06
40
12
80
64
0
A/N
orw
ay/1
01
9/2
01
72
01
7-0
2-0
6M
DC
K1
64
06
40
32
01
60
64
03
20
12
80
64
06
40
12
80
64
0
A/K
os
ice
/35
5/2
01
76
B.1
20
17
-02
-15
MD
CK
x/M
DC
K1
64
01
60
32
01
60
32
01
60
64
06
40
64
01
28
06
40
A/K
os
ice
/35
4/2
01
76
B.1
20
17
-02
-16
MD
CK
x/M
DC
K1
64
03
20
32
01
60
64
03
20
12
80
64
06
40
12
80
64
0
A/T
ori
no
/93
/20
17
6B
.12
01
7-0
2-1
7M
DC
K3
/MD
CK
16
40
64
03
20
16
06
40
32
01
28
06
40
64
01
28
06
40
A/R
he
inla
nd
-Pfa
lz/4
2/2
01
76
B.1
20
17
-02
-17
C2
/MD
CK
16
40
32
01
60
80
32
01
60
64
06
40
64
01
28
06
40
A/B
aye
rn/8
1/2
01
76
B.1
20
17
-02
-27
C1
/MD
CK
16
40
64
01
60
80
32
03
20
64
06
40
64
01
28
06
40
A/N
orw
ay/1
88
8/2
01
76
B.1
20
17
-03
-20
MD
CK
1/M
DC
K1
12
80
64
06
40
32
06
40
32
01
28
06
40
12
80
25
60
12
80
A/N
orw
ay/2
14
6/2
01
76
B.1
20
17
-04
-03
MD
CK
1/M
DC
K1
64
06
40
64
01
60
12
80
32
01
28
06
40
12
80
25
60
12
80
A/N
orw
ay/2
14
7/2
01
76
B.1
20
17
-04
-04
MD
CK
11
28
01
28
06
40
32
01
28
03
20
25
60
12
80
12
80
25
60
12
80
A/N
orw
ay/2
33
9/2
01
76
B.1
20
17
-04
-19
MD
CK
16
40
12
80
64
03
20
64
03
20
25
60
12
80
12
80
25
60
12
80
Va
cc
ine
NH
20
17
-18
Va
cc
ine
NH
20
16
-17
1 <
=
<4
0;
2 <
= <
80
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Su
pe
rsc
rip
ts r
efe
r to
an
tis
eru
m p
rop
ert
ies
(<
re
late
s t
o t
he
lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
)
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
6
Figure 1. Phylogenetic comparison of influenza A(H1N1)pdm09 HA genes
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
7
Influenza A(H3N2) virus analyses As described in many previous reports4 influenza A(H3N2) viruses continue to be difficult to characterise antigenically by HI assay due to variable agglutination of red blood cells (RBCs) from guinea pigs, turkeys and humans often with the loss of ability to agglutinate any of these RBCs. As was highlighted first in the November 2014 report5, this is a particular problem for most viruses that fall in genetic subclade 3C.2a.
Results of HI tests performed with guinea pig RBCs in the presence of 20nM oseltamivir, added to circumvent NA-mediated binding of A(H3N2) viruses to the RBCs, are shown in Tables 4-1 to 4-4. Since the February 2017 VCM report, 105 EU/EAA viruses retained sufficient HA titre to be analysed by HI assay. A further 140 viruses were successfully propagated as shown by positive neuraminidase activity but they could not be analysed by HI due to insufficient HA activity in the presence of 20nM oseltamivir.
The antiserum raised against egg-propagated A/Switzerland/9715293/2013 (3C.3a), the northern hemisphere
2015–16 vaccine component, reacted poorly with all but 10 (10%) test viruses at titres ≥eightfold reduced
compared to the homologous titre. Eight of the ten viruses have been characterised genetically to date and all eight fall within the 3C.3a subclade. However, the antiserum raised against the cell culture-propagated cultivar of A/Switzerland/9715293/2013 was able to recognise 98 (93%) test viruses at titres similar to the homologous titre of the antiserum but this antiserum had a very low titre for the homologous virus. An antiserum raised against egg-propagated A/Hong Kong/4801/2014, the virus recommended for use in vaccines for the northern hemisphere 2016–17, 2017–18 and southern hemisphere 2017 influenza seasons, recognised 102/105 (97%) test viruses at titres within fourfold compared to the titre of the antiserum for the homologous virus. Antiserum raised against the cell-propagated cultivar of A/Hong Kong/4801/2014 was slightly less effective with 90/105 (86%) giving titres within fourfold of that for the homologous virus. Similarly, an antiserum raised against another cell culture-propagated virus in clade 3C.2a, A/Hong Kong/5738/2014, recognised the test viruses well, with 103/105 (98%) of viruses recognised at a titre within fourfold of the homologous titre, 79% at a titre within twofold of the homologous titre of the antiserum. However, an antiserum raised against A/Georgia/2565/2016, another 3C.2a virus, recognised the test viruses poorly. Antisera have been raised against two reference viruses in the 3C.2a1 subclade, A/Oman/2565/2016 and A/Norway/4436/2016, but these reference viruses are unable to agglutinate red blood cells. Nevertheless, all the test viruses but two were recognised by these antisera at a range of titres within fourfold of the highest titre. The exceptions were A/Ireland/72703/2016, which was less well recognised by the antiserum raised against A/Norway/4436/2016, and A/Catalonia/93065/2016, which was less well recognised by the antisera raised against both A/Norway/4436/2016 and A/Catalonia/93065/2016 than were the other test viruses. Of the 72 viruses analysed by HI and characterised genetically, to date, 10, 23 and 39 fell within genetic subclades 3C.3a, 3C.2a and 3C.2a1 respectively.
Since 2009, seven genetic groups based on the HA gene have been defined for A(H3N2) viruses. Phylogenetic analysis of the HA genes of representative A(H3N2) viruses with recent collection dates is shown in Figure 2. The HA genes fall within clade 3C. This clade has three subdivisions: 3C.1 (represented by A/Texas/50/2012, the vaccine virus recommended for use in the 2014–15 northern hemisphere season), 3C.2 and 3C.3. Viruses in these three subdivisions had been antigenically similar. Following further diversification, in 2014 three new subclades were designated, one in subdivision 3C.2, 3C.2a, and two in 3C.3, 3C.3a and 3C.3b. Viruses in subclades 3C.2a and 3C.3a are antigenic drift variants and have circulated widely, with subclade 3C.2a viruses dominating in recent
months (Figure 2). Clusters of viruses have emerged in both subclades and one of these clusters has been designated 3C.2a1. Amino acid substitutions that define these subdivisions and subclades are:
3C.2a: N145S in HA1, and D160N in HA2, which defined clade 3C.2, plus L3I, N144S (resulting in the loss of a potential glycosylation site), F159Y, K160T (in the majority of viruses, resulting in the gain of a potential glycosylation site), N225D and Q311H in HA1, e.g. A/Hong Kong/4801/2014,
3C.2a1: those in 3C.2a, plus N171K in HA1 and I77V and G155E in HA2, e.g. A/Bolzano/7/2016 and A/Iasi/206625/2017, often with N121K in HA1, e.g. A/Scotland/63440583/2016 and A/Bulgaria/471/2017,
3C.3a: T128A (resulting in the loss of a potential glycosylation site), R142G and N145S in HA1 which defined clade 3C.3 plus A138S, F159S and N225D in HA1, many with K326R, e.g. A/Switzerland/9715293/2013 defining subclade 3C3a.
A total of 147 A(H3N2) viruses with collection dates since 1 January 2017 have been analysed genetically. One belonged to subclade 3C.3a and 146 fell within subclade 3C.2a. Of the latter, 108 were further differentiated as
subclade 3C.2a1 viruses.
_____
4 For example, the September 2013 report: European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, September 2013. Stockholm: ECDC; 2014. Available from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/influenza-virus-characterisation-sep-2013.pdf
5 European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, November 2014. Stockholm: ECDC; 2014. Available from: http://www.ecdc.europa.eu/en/publications/Publications/ERLI-Net report November 2014.pdf
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
8
The World Health Organization recommendations for the A(H3N2) component of influenza vaccines for the northern hemisphere 2016–17 [2], southern hemisphere 2017 [3] and northern hemisphere 2017–18 [4] influenza
seasons was for an A/Hong Kong/4801/2014-like (3C.2a) virus.
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
9
Table 4-1. Antigenic analysis of A(H3N2) viruses by HI (guinea pig RBC with 20nM oseltamivir)
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eA
/Te
xa
sA
/Sa
ma
raA
/Sto
ck
A/S
toc
kA
/Sw
itz
A/S
wit
zA
/HK
A/H
KA
/HK
A/G
eo
rgia
A/O
ma
nA
/No
r
info
rma
tio
nd
ate
his
tory
50
/12
73
/13
6/1
46
/14
97
15
29
3/1
39
71
52
93
/13
57
38
/14
48
01
/14
48
01
/14
53
2/1
52
58
5/1
64
43
6/1
6
Pa
ss
ag
e h
isto
ryE
gg
SIA
TS
IAT
Eg
g
SIA
TE
gg
MD
CK
MD
CK
Eg
gS
IAT
SIA
TS
IAT
Fe
rre
t n
um
be
rF
36
/12
*1F
35
/15
*1F
14
/14
*1F
20
/14
*1F
18
/15
*1F
32
/14
*1F
30
/14
*1F
43
/15
*1F
12
/15
*1F
33
/15
*1N
IB F
50
/16
*1F
03
/17
*1
Ge
ne
tic
gro
up
3C
.13
C.3
3C
.3a
3C
.3a
3C
.3a
3C
.3a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
13
C.2
a1
RE
FE
RE
NC
E V
IRU
SE
S
A/T
ex
as
/50
/20
12
3C
.12
01
2-0
4-1
5E
5/E
25
12
06
40
16
06
40
80
64
01
60
64
08
01
60
16
03
20
A/S
am
ara
/73
/20
13
3C
.32
01
3-0
3-1
2C
1/S
IAT
41
28
06
40
32
03
20
80
32
03
20
64
08
03
20
32
06
40
A/S
toc
kh
olm
/6/2
01
43
C.3
a2
01
4-0
2-0
6S
IAT
1/S
IAT
34
04
03
20
16
08
08
01
60
16
04
08
01
60
16
0
A/S
toc
kh
olm
/6/2
01
4is
ola
te 2
3C
.3a
20
14
-02
-06
E4
/E1
64
08
01
60
32
04
06
40
16
03
20
40
80
16
03
20
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
33
C.3
a2
01
3-1
2-0
6S
IAT
1/S
IAT
24
04
01
60
16
01
60
80
80
16
04
08
01
60
16
0
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
3c
lon
e 1
23
3C
.3a
20
13
-12
-06
E4
/E1
32
01
60
16
03
20
40
64
01
60
16
04
01
60
16
03
20
A/H
on
g K
on
g/5
73
8/2
01
43
C.2
a2
01
4-0
4-3
0M
DC
K1
/MD
CK
2/S
IAT
28
08
01
60
16
08
08
01
60
32
01
60
16
03
20
32
0
A/H
on
g K
on
g/4
80
1/2
01
43
C.2
a2
01
4-0
2-2
6M
DC
K4
/MD
CK
21
60
80
32
01
60
16
01
60
32
06
40
16
03
20
64
03
20
A/H
on
g K
on
g/4
80
1/2
01
4is
ola
te 1
3C
.2a
20
14
-02
-26
E6
/E2
40
80
40
40
40
40
16
03
20
16
03
20
64
01
60
A/G
eo
rgia
/53
2/2
01
5p
laq
20
3C
.2a
20
15
-03
-09
SIA
T1
/SIA
T5
16
08
03
20
16
08
08
03
20
32
01
60
12
80
32
03
20
TE
ST
VIR
US
ES
A/S
toc
kh
olm
/48
/20
16
3C
.2a
un
kn
ow
nM
DC
K1
/SIA
T1
40
40
16
08
04
04
08
03
20
80
80
16
01
60
A/C
ze
ch
Re
pu
blic
/17
8/2
01
73
C.2
a1
un
kn
ow
nM
DC
Kx
/SIA
T1
<<
40
40
40
<4
08
04
04
01
60
80
A/L
yo
n/2
20
7/2
01
63
C.2
a1
20
16
-10
-24
MD
CK
3/S
IAT
14
04
01
60
80
80
40
80
32
08
01
60
16
01
60
A/P
oit
iers
/22
38
/20
16
3C
.2a
12
01
6-1
1-0
1M
DC
K3
/SIA
T1
80
80
32
01
60
16
08
01
60
32
01
60
16
03
20
32
0
A/C
lerm
on
t F
err
an
d/2
22
7/2
01
63
C.2
a1
20
16
-11
-02
MD
CK
2/S
IAT
1<
40
16
08
04
04
08
01
60
40
80
80
16
0
A/P
oit
iers
/22
39
/20
16
3C
.2a
20
16
-11
-02
MD
CK
3/S
IAT
14
04
01
60
80
40
40
80
16
08
01
60
16
01
60
A/S
ac
hs
en
/74
/20
16
3C
.2a
12
01
6-1
1-0
7C
1/S
IAT
14
0<
16
08
08
0<
80
16
08
04
01
60
16
0
A/S
toc
kh
olm
/42
/20
16
3C
.2a
12
01
6-1
1-1
0M
DC
K1
/SIA
T1
40
40
16
08
04
04
08
03
20
80
80
16
01
60
A/L
atv
ia/1
1-0
72
12
5/2
01
63
C.2
a1
20
16
-11
-28
C2
/SIA
T1
40
40
80
80
40
80
80
16
08
08
08
08
0
A/A
us
tria
/95
69
28
/20
16
3C
.2a
12
01
6-1
1-3
0C
1/S
IAT
18
08
01
60
16
08
08
08
03
20
80
16
01
60
16
0
A/H
un
ga
ry/1
75
/20
16
3C
.2a
20
16
-12
-02
MD
CK
1/S
IAT
14
0<
80
80
40
<8
08
04
04
01
60
16
0
A/A
us
tria
/95
73
44
/20
16
3C
.2a
12
01
6-1
2-0
4C
1/S
IAT
1<
<1
60
40
40
<4
01
60
40
40
80
16
0
A/A
us
tria
/95
78
60
/20
16
3C
.2a
12
01
6-1
2-0
6C
2/S
IAT
14
04
01
60
80
80
40
80
16
08
08
01
60
16
0
A/L
atv
ia/1
2-0
20
47
4/2
01
63
C.2
a1
20
16
-12
-08
C2
/SIA
T1
40
40
80
80
40
40
80
32
08
08
01
60
80
A/B
aye
rn/7
6/2
01
63
C.2
a2
01
6-1
2-1
3C
1/S
IAT
14
04
01
60
80
16
04
01
60
16
08
08
03
20
32
0
A/H
un
ga
ry/1
88
/20
16
3C
.2a
12
01
6-1
2-1
3M
DC
K1
/SIA
T1
40
<4
04
04
0<
40
40
<4
08
08
0
A/H
un
ga
ry/1
91
/20
16
3C
.2a
12
01
6-1
2-1
3M
DC
K1
/SIA
T1
40
40
16
08
04
04
08
01
60
80
80
16
01
60
A/H
un
ga
ry/2
02
/20
16
3C
.2a
20
16
-12
-14
MD
CK
1/S
IAT
14
0<
80
40
40
<8
08
0<
40
80
80
A/C
ze
ch
Re
pu
blic
/16
9/2
01
63
C.2
a1
20
16
-12
-14
MD
CK
2/S
IAT
14
0<
16
08
04
04
01
60
16
08
08
01
60
16
0
A/S
we
de
n/1
53
/20
16
3C
.2a
20
16
-12
-16
MD
CK
1/S
IAT
1<
<1
60
40
40
<4
01
60
40
80
16
08
0
A/L
ux
em
bo
urg
/63
72
2/2
01
63
C.2
a1
20
16
-12
-16
SIA
T2
80
40
32
08
01
60
40
16
01
60
80
16
03
20
32
0
A/S
we
de
n/1
57
/20
16
3C
.2a
12
01
6-1
2-1
7M
DC
K1
/SIA
T1
40
<1
60
80
80
<8
01
60
40
40
16
01
60
A/C
ze
ch
Re
pu
blic
/17
6/2
01
63
C.2
a2
01
6-1
2-1
9M
DC
K2
/SIA
T1
40
<1
60
40
40
40
16
01
60
40
16
01
60
16
0
A/G
ree
ce
/72
6/2
01
63
C.2
a2
01
6-1
2-1
9S
IAT
14
04
01
60
80
40
<1
60
16
08
08
01
60
16
0
A/Ire
lan
d/0
00
98
/20
16
3C
.3a
20
16
-12
-29
C1
/SIA
T1
40
40
32
01
60
80
80
80
80
40
80
80
80
A/Ire
lan
d/8
61
10
/20
16
3C
.2a
12
01
6-1
2-2
9C
1/S
IAT
1<
<4
04
0<
<4
01
60
40
40
80
80
A/Ire
lan
d/0
04
92
/20
17
3C
.2a
12
01
7-0
1-0
2C
1/S
IAT
14
04
08
08
04
04
08
01
60
80
16
01
60
16
0
A/S
lov
en
ia/5
3/2
01
73
C.2
a2
01
7-0
1-0
4M
DC
K1
/SIA
T1
40
40
16
08
04
04
08
01
60
40
80
80
16
0
A/G
ree
ce
/35
/20
17
3C
.2a
12
01
7-0
1-1
0S
IAT
24
0<
80
40
40
<8
01
60
80
40
16
01
60
A/A
the
ns
GR
/49
6/2
01
73
C.2
a2
01
7-0
1-1
7S
IAT
14
04
01
60
80
80
40
16
01
60
80
80
16
03
20
A/A
the
ns
GR
/49
9/2
01
73
C.2
a1
20
17
-01
-17
SIA
T1
40
40
16
08
08
04
01
60
32
08
08
01
60
16
0
A/A
the
ns
GR
/51
0/2
01
73
C.2
a1
20
17
-01
-18
SIA
T1
80
40
32
01
60
16
08
01
60
32
08
01
60
32
03
20
A/A
the
ns
GR
/56
6/2
01
73
C.2
a1
20
17
-01
-19
SIA
T1
40
40
16
08
04
04
08
01
60
80
80
16
01
60
*S
up
ers
cri
pts
re
fer
to a
nti
se
rum
pro
pe
rtie
s (
< r
ela
tes
to
th
e lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
) 1 <
= <
40
Va
cc
ine
Se
qu
en
ce
in
ph
ylo
ge
ne
tic
tre
e
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
10
Table 4-2. Antigenic analysis of A(H3N2) viruses by HI (guinea pig RBC with 20nM oseltamivir)
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eA
/Te
xa
sA
/Sa
ma
raA
/Sto
ck
A/S
toc
kA
/Sw
itz
A/S
wit
zA
/HK
A/H
KA
/HK
A/G
eo
rgia
A/O
ma
nA
/No
r
info
rma
tio
nd
ate
his
tory
50
/12
73
/13
6/1
46
/14
97
15
29
3/1
39
71
52
93
/13
57
38
/14
48
01
/14
48
01
/14
53
2/1
52
58
5/1
64
43
6/1
6
Pa
ss
ag
e h
isto
ryE
gg
SIA
TS
IAT
Eg
g
SIA
TE
gg
MD
CK
MD
CK
Eg
gS
IAT
SIA
TS
IAT
Fe
rre
t n
um
be
rF
08
/14
*1F
35
/15
*1F
14
/14
*1F
20
/14
*1F
18
/15
*1F
32
/14
*1F
30
/14
*1F
43
/15
*1F
12
/15
*1F
33
/15
*1N
IB F
50
/16
*1F
03
/17
*1
Ge
ne
tic
gro
up
3C
.13
C.3
3C
.3a
3C
.3a
3C
.3a
3C
.3a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
13
C.2
a1
RE
FE
RE
NC
E V
IRU
SE
S
A/T
ex
as
/50
/20
12
3C
.12
01
2-0
4-1
5E
5/E
22
56
06
40
16
06
40
40
64
01
60
32
08
03
20
16
03
20
A/S
am
ara
/73
/20
13
3C
.32
01
3-0
3-1
2C
1/S
IAT
41
28
01
28
06
40
64
01
60
64
03
20
12
80
16
06
40
64
01
28
0
A/S
toc
kh
olm
/6/2
01
43
C.3
a2
01
4-0
2-0
6S
IAT
1/S
IAT
38
08
03
20
32
01
60
16
01
60
32
08
01
60
32
03
20
A/S
toc
kh
olm
/6/2
01
4is
ola
te 2
3C
.3a
20
14
-02
-06
E4
/E1
16
08
08
03
20
40
64
08
03
20
40
80
16
03
20
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
33
C.3
a2
01
3-1
2-0
6S
IAT
1/S
IAT
34
04
03
20
16
01
60
80
80
16
04
01
60
16
03
20
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
3c
lon
e 1
23
3C
.3a
20
13
-12
-06
E4
/E1
16
01
60
16
03
20
80
64
01
60
32
04
01
60
32
03
20
A/H
on
g K
on
g/5
73
8/2
01
43
C.2
a2
01
4-0
4-3
0M
DC
K1
/MD
CK
2/S
IAT
24
04
03
20
80
16
08
03
20
64
01
60
16
03
20
64
0
A/H
on
g K
on
g/4
80
1/2
01
43
C.2
a2
01
4-0
2-2
6M
DC
K4
/MD
CK
28
08
01
60
16
08
08
01
60
32
01
60
16
01
60
32
0
A/H
on
g K
on
g/4
80
1/2
01
4is
ola
te 1
3C
.2a
20
14
-02
-26
E6
/E2
40
80
40
40
40
40
16
06
40
16
06
40
32
01
60
A/G
eo
rgia
/53
2/2
01
5p
laq
20
3C
.2a
20
15
-03
-09
SIA
T1
/SIA
T5
40
80
32
03
20
16
01
60
32
06
40
80
12
80
32
06
40
A/N
orw
ay/4
46
5/2
01
6is
ola
te 2
clo
ne
27
E6
<<
<4
04
0<
16
01
60
80
12
80
32
01
60
TE
ST
VIR
US
ES
A/L
ux
em
bo
urg
/62
06
2/2
01
63
C.2
a1
20
16
-12
-06
MD
CK
1/S
IAT
14
04
01
60
80
40
80
80
32
08
01
60
16
01
60
A/L
ux
em
bo
urg
/63
25
7/2
01
62
01
6-1
2-1
2M
DC
K1
/SIA
T1
40
40
16
01
60
40
40
80
32
08
01
60
16
01
60
A/Ic
ela
nd
/65
/20
16
3C
.2a
12
01
6-1
2-1
2M
DC
K1
/SIA
T1
40
40
16
08
04
04
01
60
16
08
01
60
16
01
60
A/Ic
ela
nd
/66
/20
16
3C
.2a
20
16
-12
-14
MD
CK
1/S
IAT
14
04
01
60
80
40
40
16
01
60
80
16
01
60
16
0
A/Ic
ela
nd
/68
/20
16
3C
.3a
20
16
-12
-15
MD
CK
1/S
IAT
18
08
06
40
32
01
60
16
01
60
32
01
60
16
03
20
32
0
A/Ic
ela
nd
/70
/20
16
3C
.2a
20
16
-12
-19
MD
CK
1/S
IAT
14
04
01
60
80
40
40
16
01
60
80
32
01
60
16
0
A/Ic
ela
nd
/72
/20
16
3C
.2a
20
16
-12
-19
MD
CK
1/S
IAT
14
04
01
60
80
40
40
16
03
20
80
16
01
60
16
0
A/Ic
ela
nd
/74
/20
16
3C
.3a
20
16
-12
-21
MD
CK
1/S
IAT
14
04
03
20
16
08
08
01
60
16
08
01
60
16
01
60
A/Ic
ela
nd
/76
/20
16
3C
.2a
12
01
6-1
2-2
4M
DC
K1
/SIA
T1
40
40
16
08
04
04
08
01
60
80
16
01
60
16
0
A/Ic
ela
nd
/78
/20
16
3C
.2a
20
16
-12
-26
MD
CK
1/S
IAT
14
04
01
60
80
40
40
16
01
60
80
16
01
60
32
0
A/P
ola
nd
/30
48
4/2
01
63
C.2
a2
01
6-1
2-2
8S
IAT
24
04
01
60
80
80
40
80
16
04
08
01
60
16
0
*S
up
ers
cri
pts
re
fer
to a
nti
se
rum
pro
pe
rtie
s (
< r
ela
tes
to
th
e lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
) 1 <
= <
40
Va
cc
ine
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
11
Table 4-3. Antigenic analysis of A(H3N2) viruses by HI (guinea pig RBC with 20nM oseltamivir)
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eA
/Te
xa
sA
/Sa
ma
raA
/Sto
ck
A/S
toc
kA
/Sw
itz
A/S
wit
zA
/HK
A/H
KA
/HK
A/G
eo
rgia
A/O
ma
nA
/No
r
info
rma
tio
nd
ate
his
tory
50
/12
73
/13
6/1
46
/14
97
15
29
3/1
39
71
52
93
/13
57
38
/14
48
01
/14
48
01
/14
53
2/1
52
58
5/1
64
43
6/1
6
Pa
ss
ag
e h
isto
ryE
gg
SIA
TS
IAT
Eg
g
SIA
TE
gg
MD
CK
MD
CK
Eg
gS
IAT
SIA
TS
IAT
Fe
rre
t n
um
be
rF
08
/14
*1F
35
/15
*1F
14
/14
*1F
20
/14
*1F
18
/15
*1F
73
/16
*1F
30
/14
*1F
43
/15
*1F
12
/15
*1F
33
/15
*1N
IB F
50
/16
*1F
03
/17
*1
Ge
ne
tic
gro
up
3C
.13
C.3
3C
.3a
3C
.3a
3C
.3a
3C
.3a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
13
C.2
a1
RE
FE
RE
NC
E V
IRU
SE
S
A/T
ex
as
/50
/20
12
3C
.12
01
2-0
4-1
5E
5/E
22
56
06
40
16
06
40
80
32
01
60
32
08
03
20
16
06
40
A/S
am
ara
/73
/20
13
3C
.32
01
3-0
3-1
2C
1/S
IAT
46
40
64
03
20
32
01
60
32
03
20
64
01
60
64
03
20
64
0
A/S
toc
kh
olm
/6/2
01
43
C.3
a2
01
4-0
2-0
6S
IAT
1/S
IAT
34
04
03
20
16
01
60
80
16
01
60
80
16
01
60
16
0
A/S
toc
kh
olm
/6/2
01
4is
ola
te 2
3C
.3a
20
14
-02
-06
E4
/E1
16
01
60
16
03
20
80
32
01
60
32
04
08
01
60
32
0
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
33
C.3
a2
01
3-1
2-0
6S
IAT
1/S
IAT
3<
40
16
08
01
60
80
80
80
40
80
16
01
60
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
3c
lon
e 1
23
3C
.3a
20
13
-12
-06
E4
/E1
80
16
01
60
32
08
06
40
16
03
20
40
16
01
60
32
0
A/H
on
g K
on
g/5
73
8/2
01
43
C.2
a2
01
4-0
4-3
0M
DC
K1
/MD
CK
2/S
IAT
38
04
01
60
16
08
04
01
60
64
01
60
32
03
20
32
0
A/H
on
g K
on
g/4
80
1/2
01
43
C.2
a2
01
4-0
2-2
6M
DC
K4
/MD
CK
18
08
01
60
16
08
08
01
60
64
01
60
32
03
20
32
0
A/H
on
g K
on
g/4
80
1/2
01
4is
ola
te 1
3C
.2a
20
14
-02
-26
E6
/E2
40
80
80
80
40
<3
20
64
01
60
64
06
40
32
0
A/G
eo
rgia
/53
2/2
01
5p
laq
20
3C
.2a
20
15
-03
-09
SIA
T1
/SIA
T5
80
80
16
01
60
80
80
16
03
20
80
64
03
20
32
0
TE
ST
VIR
US
ES
A/Ire
lan
d/7
22
54
/20
16
3C
.3a
20
16
-11
-12
C1
/SIA
T1
40
40
32
01
60
16
01
60
80
16
08
08
01
60
16
0
A/Ire
lan
d/7
27
03
/20
16
3C
.2a
12
01
6-1
1-1
4C
1/S
IAT
1<
<<
<<
<4
01
60
40
40
80
40
A/C
ata
lon
ia/9
30
5S
/20
16
3C
.2a
12
01
6-1
1-2
4C
0/S
IAT
14
0<
16
08
04
04
08
01
60
80
40
16
01
60
A/Ire
lan
d/7
62
55
/20
16
3C
.2a
12
01
6-1
1-2
9C
2/S
IAT
1<
<<
<<
<<
40
<<
40
40
A/B
elg
ium
/G0
68
7/2
01
63
C.2
a2
01
6-1
1-3
0S
IAT
14
04
01
60
80
40
40
16
01
60
80
80
32
03
20
A/Ire
lan
d/7
87
17
/20
16
3C
.3a
20
16
-12
-06
C1
/SIA
T1
80
80
64
03
20
16
01
60
16
01
60
80
80
16
01
60
A/Ire
lan
d/8
09
71
/20
16
3C
.2a
12
01
6-1
2-1
5C
1/S
IAT
14
04
08
01
60
40
40
80
16
08
08
01
60
16
0
A/Ire
lan
d/8
11
04
/20
16
3C
.3a
20
16
-12
-15
C1
/SIA
T1
80
80
32
06
40
16
03
20
16
03
20
16
01
60
32
03
20
A/Ire
lan
d/8
13
54
/20
16
3C
.2a
20
16
-12
-17
C2
/SIA
T1
40
<8
01
60
40
40
80
16
08
01
60
16
01
60
A/Ire
lan
d/8
11
80
/20
16
3C
.2a
12
01
6-1
2-1
9C
1/S
IAT
14
0<
80
16
04
04
08
03
20
40
80
16
01
60
A/Ire
lan
d/8
19
20
/20
16
3C
.3a
20
16
-12
-21
C1
/SIA
T1
40
40
32
06
40
16
01
60
16
01
60
80
80
16
01
60
A/Ire
lan
d/8
23
26
/20
16
3C
.3a
20
16
-12
-21
C1
/SIA
T1
40
40
32
06
40
16
01
60
16
01
60
80
80
16
01
60
A/C
ata
lon
ia/9
41
5S
/20
17
3C
.2a
20
16
-12
-21
C0
/SIA
T1
40
40
16
08
04
04
08
01
60
80
40
16
01
60
A/Ire
lan
d/8
27
45
/20
16
3C
.3a
20
16
-12
-22
C1
/SIA
T1
80
80
64
03
20
16
01
60
16
01
60
80
80
16
01
60
A/B
elg
ium
/G0
02
4/2
01
73
C.2
a1
20
17
-01
-03
SIA
T1
40
40
16
08
08
04
01
60
32
08
01
60
16
01
60
A/B
elg
ium
/G0
04
2/2
01
73
C.2
a1
20
17
-01
-05
SIA
T1
40
<1
60
80
40
40
16
01
60
80
80
16
01
60
A/L
atv
ia/0
1-0
24
57
5/2
01
73
C.2
a2
01
7-0
1-1
0C
2/S
IAT
18
08
01
60
32
01
60
80
16
03
20
80
16
03
20
32
0
A/C
yp
rus
/F4
9/2
01
73
C.2
a1
20
17
-01
-12
SIA
T1
40
<1
60
80
40
40
80
16
08
04
01
60
16
0
A/A
the
ns
GR
/56
3/2
01
73
C.2
a1
20
17
-01
-19
SIA
T1
40
<1
60
40
80
40
80
16
08
08
01
60
16
0
A/N
orw
ay/4
84
/20
17
3C
.2a
20
17
-01
-22
SIA
T1
/SIA
T1
<<
16
08
0<
<4
08
04
01
60
16
01
60
A/C
yp
rus
/F1
48
/20
17
3C
.2a
12
01
7-0
1-2
6S
IAT
14
04
08
08
04
04
08
03
20
80
80
16
01
60
A/C
ata
lon
ia/3
50
96
91
NS
/20
17
3C
.2a
20
17
-02
-02
C0
/SIA
T1
40
40
16
08
04
04
08
01
60
80
80
16
01
60
A/N
orw
ay/1
12
0/2
01
73
C.2
a2
01
7-0
2-1
1S
IAT
1/S
IAT
1<
<1
60
80
40
40
80
16
04
01
60
16
01
60
A/L
atv
ia/0
2-0
57
39
2/2
01
7
3C
.2a
12
01
7-0
2-1
7C
1/S
IAT
18
04
01
60
32
01
60
80
16
03
20
16
08
03
20
32
0
A/L
atv
ia/0
2-0
56
74
8/2
01
73
C.2
a2
01
7-0
2-2
0C
2/S
IAT
18
04
01
60
16
08
08
01
60
32
08
03
20
16
01
60
A/L
atv
ia/0
2-0
62
18
7/2
01
7
20
17
-02
-22
C2
/SIA
T1
80
80
16
03
20
80
80
16
03
20
80
16
03
20
32
0
A/Ic
ela
nd
/40
/20
17
3C
.2a
12
01
7-0
2-2
2M
DC
K1
/SIA
T1
<<
16
04
04
0<
16
08
04
08
08
01
60
A/Ic
ela
nd
/64
/20
17
3C
.2a
12
01
7-0
3-0
8M
DC
K1
/SIA
T1
<<
16
04
04
0<
40
16
04
04
08
01
60
A/Ic
ela
nd
/69
/20
17
3C
.3a
20
17
-03
-09
MD
CK
1/S
IAT
14
04
03
20
16
08
01
60
80
16
08
08
01
60
16
0
A/L
atv
ia/0
4-0
03
62
6/2
01
73
C.2
a1
20
17
-04
-03
C1
/SIA
T1
80
40
16
01
60
80
80
16
03
20
80
80
16
01
60
Su
pe
rsc
rip
ts r
efe
r to
an
tis
eru
m p
rop
ert
ies
(<
re
late
s t
o t
he
lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
) 1 <
= <
40
Va
cc
ine
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
e
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
12
Table 4-4. Antigenic analysis of A(H3N2) viruses by HI (guinea pig RBC with 20nM oseltamivir)
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eA
/Te
xa
sA
/Sa
ma
raA
/Sto
ck
A/S
toc
kA
/Sw
itz
A/S
wit
zA
/HK
A/H
KA
/HK
A/G
eo
rgia
A/O
ma
nA
/No
r
info
rma
tio
nd
ate
his
tory
50
/12
73
/13
6/1
46
/14
97
15
29
3/1
39
71
52
93
/13
57
38
/14
48
01
/14
48
01
/14
53
2/1
52
58
5/1
64
43
6/1
6
Pa
ss
ag
e h
isto
ryE
gg
SIA
TS
IAT
Eg
g
SIA
TE
gg
MD
CK
MD
CK
Eg
gS
IAT
SIA
TS
IAT
Fe
rre
t n
um
be
rF
08
/14
*1F
35
/15
*1F
14
/14
*1F
20
/14
*1F
18
/15
*1F
73
/16
*1F
30
/14
*1F
43
/15
*1F
12
/15
*1F
33
/15
*1N
IB F
50
/16
*1F
03
/17
*1
Ge
ne
tic
gro
up
3C
.13
C.3
3C
.3a
3C
.3a
3C
.3a
3C
.3a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
3C
.2a
13
C.2
a1
RE
FE
RE
NC
E V
IRU
SE
S
A/T
ex
as
/50
/20
12
3C
.12
01
2-0
4-1
5E
5/E
21
28
06
40
16
06
40
40
32
01
60
32
08
01
60
16
03
20
A/S
am
ara
/73
/20
13
3C
.32
01
3-0
3-1
2C
1/S
IAT
46
40
64
06
40
64
01
60
32
03
20
12
80
16
03
20
32
06
40
A/S
toc
kh
olm
/6/2
01
43
C.3
a2
01
4-0
2-0
6S
IAT
1/S
IAT
28
04
03
20
16
01
60
16
01
60
16
08
08
01
60
16
0
A/S
toc
kh
olm
/6/2
01
4is
ola
te 2
3C
.3a
20
14
-02
-06
E4
/E1
16
08
01
60
32
08
03
20
16
03
20
40
40
16
03
20
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
33
C.3
a2
01
3-1
2-0
6S
IAT
1/S
IAT
3<
<3
20
80
80
80
80
80
40
40
80
16
0
A/S
wit
ze
rla
nd
/97
15
29
3/2
01
3c
lon
e 1
23
3C
.3a
20
13
-12
-06
E4
/E1
16
01
60
16
03
20
40
64
01
60
32
04
08
01
60
32
0
A/H
on
g K
on
g/5
73
8/2
01
43
C.2
a2
01
4-0
4-3
0M
DC
K1
/MD
CK
2/S
IAT
38
01
60
32
01
60
80
80
32
06
40
16
01
60
32
03
20
A/H
on
g K
on
g/4
80
1/2
01
43
C.2
a2
01
4-0
2-2
6M
DC
K4
/MD
CK
18
08
01
60
16
08
08
01
60
64
01
60
16
01
60
16
0
A/H
on
g K
on
g/4
80
1/2
01
4is
ola
te 1
3C
.2a
20
14
-02
-26
E6
/E2
40
80
40
40
40
40
32
06
40
16
03
20
64
01
60
A/G
eo
rgia
/53
2/2
01
5p
laq
20
3C
.2a
20
15
-03
-09
SIA
T1
/SIA
T5
80
80
16
01
60
80
80
16
03
20
16
06
40
32
03
20
TE
ST
VIR
US
ES
A/L
ith
ua
nia
/67
35
/20
17
un
kn
ow
nM
DC
K2
/SIA
T1
<<
16
04
0<
<4
04
04
04
08
01
60
A/L
ith
ua
nia
/76
12
/20
17
un
kn
ow
nM
DC
K2
/SIA
T1
<<
80
40
40
<8
01
60
40
40
80
80
A/B
ulg
ari
a/2
/20
17
20
17
-01
-02
SIA
T2
/SIA
T1
40
40
32
08
08
08
01
60
16
01
60
80
32
03
20
A/B
ulg
ari
a/5
6/2
01
72
01
7-0
1-0
4S
IAT
2/S
IAT
14
0<
16
08
0<
<1
60
16
04
04
08
01
60
A/B
ulg
ari
a/1
32
/20
17
20
17
-01
-06
SIA
T2
/SIA
T1
40
80
32
01
60
80
80
16
03
20
16
08
03
20
32
0
A/B
ulg
ari
a/3
01
/20
17
20
17
-01
-09
SIA
T2
/SIA
T1
40
80
32
01
60
80
80
16
03
20
16
08
03
20
32
0
A/B
ulg
ari
a/1
82
/20
17
20
17
-01
-10
SIA
T2
/SIA
T1
80
40
32
01
60
80
80
16
03
20
16
08
03
20
32
0
A/S
ac
hs
en
/4/2
01
72
01
7-0
1-1
0C
1/S
IAT
14
04
08
08
04
04
01
60
16
08
08
01
60
16
0
A/B
ulg
ari
a/2
52
/20
17
20
17
-01
-12
SIA
T2
/SIA
T1
40
40
32
08
08
04
01
60
16
08
08
03
20
32
0
A/B
erl
in/9
/20
17
20
17
-01
-16
C1
/SIA
T1
<<
16
04
0<
<8
08
08
0<
16
01
60
A/P
ola
nd
/41
2/2
01
72
01
7-0
1-1
8S
IAT
14
04
01
60
80
40
40
16
03
20
80
80
16
01
60
A/P
ola
nd
/55
5/2
01
72
01
7-0
1-2
4S
IAT
14
04
08
08
04
04
01
60
16
08
01
60
16
01
60
A/B
ulg
ari
a/3
73
/20
17
20
17
-01
-24
SIA
T2
/SIA
T1
40
40
32
01
60
80
80
32
01
60
80
80
32
03
20
A/H
es
se
n/1
4/2
01
72
01
7-0
1-2
6C
1/S
IAT
14
04
03
20
80
40
80
16
01
60
80
40
16
01
60
A/B
ulg
ari
a/4
27
/20
17
20
17
-01
-30
SIA
T2
/SIA
T1
<<
16
08
04
0<
80
80
40
40
16
01
60
A/B
ulg
ari
a/4
14
/20
17
20
17
-02
-01
SIA
T2
/SIA
T1
<<
80
80
40
<8
08
04
08
08
01
60
A/Ic
ela
nd
/18
/20
17
20
17
-02
-13
MD
CK
1/M
DC
K2
40
80
64
03
20
16
01
60
16
01
60
80
80
16
01
60
A/Ic
ela
nd
/27
/20
17
20
17
-02
-16
MD
CK
1/S
IAT
1<
40
16
01
60
40
80
80
80
40
40
80
80
A/Ic
ela
nd
/23
/20
17
20
17
-02
-16
MD
CK
1/S
IAT
14
04
03
20
16
08
08
08
08
04
04
08
08
0
A/Ic
ela
nd
/31
/20
17
20
17
-02
-19
MD
CK
1/S
IAT
1<
40
16
01
60
40
80
80
80
40
40
80
80
A/L
ith
ua
nia
/61
65
/20
17
20
17
-02
-20
MD
CK
2/S
IAT
18
08
01
60
80
80
80
16
03
20
80
64
03
20
32
0
A/L
ith
ua
nia
/65
83
/20
17
20
17
-02
-21
MD
CK
2/S
IAT
14
08
08
08
04
04
01
60
32
08
01
60
16
03
20
A/Ic
ela
nd
/37
/20
17
20
17
-02
-21
MD
CK
1/S
IAT
14
04
03
20
16
08
01
60
80
16
08
08
01
60
16
0
A/Ic
ela
nd
/36
/20
17
20
17
-02
-21
MD
CK
1/S
IAT
14
0<
16
08
04
04
01
60
16
08
04
01
60
16
0
A/N
orw
ay/1
48
1/2
01
72
01
7-0
2-2
7S
IAT
14
04
01
60
80
40
40
16
01
60
80
80
16
01
60
A/L
ith
ua
nia
/77
03
/20
17
20
17
-02
-27
MD
CK
2/S
IAT
14
04
08
08
08
0<
80
16
08
04
08
01
60
A/N
orw
ay/1
47
7/2
01
72
01
7-0
3-0
4S
IAT
14
0<
16
08
04
04
08
01
60
40
80
16
01
60
A/L
ith
ua
nia
/79
06
/20
17
20
17
-03
-06
MD
CK
2/S
IAT
14
04
01
60
80
80
80
16
01
60
16
03
20
32
03
20
A/N
orw
ay/2
40
0/2
01
72
01
7-0
4-2
8S
IAT
1/S
IAT
18
08
03
20
16
08
08
01
60
64
01
60
80
16
01
60
A/J
ord
an
/20
15
7/2
01
72
01
7-0
4-2
2S
IAT
28
08
01
60
16
08
08
08
01
60
80
80
32
03
20
A/N
orw
ay/2
62
9/2
01
72
01
7-0
5-0
4S
IAT
11
60
80
64
01
60
16
08
03
20
32
03
20
16
03
20
32
0
*S
up
ers
cri
pts
re
fer
to a
nti
se
rum
pro
pe
rtie
s (
< r
ela
tes
to
th
e lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
) 1 <
= <
40
Va
cc
ine
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
13
Figure 2. Phylogenetic comparison of influenza A(H3N2) HA genes
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
14
Influenza B virus analyses EU/EEA countries have provided 137 influenza type B-positive specimens with collection dates after 31 December 2016: 134 were ascribed to a lineage, 52 B/Victoria-lineage and 82 B/Yamagata-lineage (Table 2).
Influenza B – Victoria lineage
Since the February VCM [14] report 32 viruses of the B/Victoria lineage have been characterised antigenically. All viruses sequenced to date belonged to genetic clade 1A and HI results are shown in Tables 5-1 to 5-3.
Most of the test viruses showed similar HI reactivity patterns to those observed throughout the 2014–15 and 2015–16 influenza seasons. All but one of the test viruses were recognised poorly by antisera raised against the egg-propagated vaccine virus, B/Brisbane/60/2008, recommended for use in both trivalent and quadrivalent vaccines. B/Rheinland-Pfalz/43/2016 was recognised well by the antiserum raised against B/Brisbane/60/2008 and was shown to be identical in sequence to the B-Victoria lineage vaccine component and is most likely to be as a result of the recovery of the influenza B component of the live attenuated influenza vaccine. The remaining 31 test viruses were generally not recognised well by post-infection ferret antisera raised against reference viruses propagated in eggs (B/Malta/636714/2011, B/Johannesburg/3964/2012 and B/South Australia/81/2012) although the antiserum raised against B/South Australia/81/2012 recognised 24/31 (77%) test viruses at a titre within fourfold of the homologous titre of the antiserum. By contrast, 31 test viruses showed reactivity within fourfold –the majority within twofold – of the titres for the corresponding homologous viruses with antisera raised against viruses that are considered to be surrogate tissue culture-propagated antigens representing the egg-propagated B/Brisbane/60/2008 prototype virus. These antisera were raised against tissue culture propagated viruses B/Hong Kong/514/2009 (clade 1B), B/Formosa/V2367/2012, B/Ireland/3154/2016 and B/Nordrhein-Westfalen/1/2016 (all clade 1A). Notably, B/Norway/2409/2017 showed no reactivity with post-infection ferret antisera raised against egg-propagated or cell-propagated viruses and a very low reaction with the hyperimmune sheep antiserum pool raised against B/Brisbane/60/2008. B/Norway/2409/2017 has a deletion of two amino acids at residues 162 and 163 in the HA1 glycoprotein; several other examples of this variant have been seen elsewhere, most notably in North America.
Phylogenetic analysis of the HA gene of representative B/Victoria lineage viruses is shown in Figure 3. Viruses from Europe, and elsewhere, continue to have HA genes that fall into the B/Brisbane/60/2008 clade (clade 1A) and the majority remain antigenically similar to the vaccine virus B/Brisbane/60/2008. The great majority of viruses, with collection dates since October 2015, fall in a major subcluster defined by amino acid substitutions I117V, N129D and V146I within clade 1A. The viruses with the 162-163 HA1 deletion have additional substitutions D129G, I180V in HA1 and R151K in HA2.
These results, linked with the rise in the proportion of B/Victoria-lineage viruses seen since 2015, supported the continued recommendation to include B/Brisbane/60/2008 in trivalent and quadrivalent influenza vaccines for the southern hemisphere 2017 [3] and northern hemisphere 2017–2018 [4].
Influenza B – Yamagata lineage HI results for 58 B/Yamagata-lineage test virus analysed since the February VCM [14] report are shown in Tables 6-1 to 6-3. All the viruses sequenced belonged to genetic clade 3.
Antisera raised against egg-propagated B/Phuket/3073/2013, recommended for inclusion in quadrivalent influenza vaccines since the southern hemisphere 2016 season, recognised 42/58 (72%) test viruses at titres within fourfold of the titre of the virus for the homologous virus. However, an antiserum raised against the cell culture-propagated cultivar of B/Phuket/3073/2013 recognised only 57% of viruses at titres within fourfold of the homologous titre of the antiserum. An antiserum raised against the former vaccine virus egg-propagated B/Wisconsin/1/2010 recognised a higher proportion of the test viruses, 77% (45 of 58), at a titre within fourfold of the homologous titre of the antiserum, and, similarly, antisera raised against egg-propagated B/Stockholm/12/2011 and egg-propagated B/Hong Kong/3417/2014 recognised 91% (53 of 58) and 100% (all 58), respectively, of the test virus at titres within fourfold of the respective homologous titres of the antisera.
An antiserum raised against another formerly recommended vaccine virus egg-propagated B/Massachusetts/02/2012, a clade 2 virus, recognised the test viruses less well, with only 20 of the 58 viruses (34%) being recognised at titres within fourfold of the homologous titre of the antiserum. However, the test viruses were recognised better by the cell culture-propagated cultivar of B/Massachusetts/02/2012 with 38 of 58 test viruses (66%) of test viruses being recognised at titres within fourfold of the homologous titre of the antiserum. An antiserum raised against another cell culture-propagated clade 2 virus B/Estonia/55669/2011 recognised 27 of 58 test viruses (47%) of test viruses at titres within fourfold of the homologous titre of the antiserum.
Figure 4 shows a phylogenetic analysis of the HA genes of representative B/Yamagata-lineage viruses. Worldwide, the vast majority of HA genes from recently collected viruses have fallen in the B/Wisconsin/1/2010–B/Phuket/3073/2013 clade (clade 3), with the great majority falling in a subgroup defined by HA1 L172Q and
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
15
M251V amino acid substitutions. Two viruses, annotated in the phylogenetic tree, are reassortants carrying NA genes normally associated with the B/Victoria-lineage.
Based on such results, a B/Phuket/3073/2013-like virus was recommended for inclusion in quadrivalent vaccines for the 2017–2018 northern hemisphere [4] season.
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
16
Table 5-1. Antigenic analysis of influenza B/Victoria-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Bri
sB
/Ma
lB
/Bri
sB
/Ma
lta
B/J
hb
B/F
or
B/S
th A
us
B/H
KB
/Ire
lan
dB
/No
rd-W
es
t
info
rma
tio
nd
ate
his
tory
60
/08
25
06
/04
60
/08
63
67
14
/11
39
64
/12
V2
36
7/1
28
1/1
25
14
/09
31
54
/16
1/1
6
Pa
ss
ag
e h
isto
ryE
gg
Eg
gE
gg
Eg
gE
gg
MD
CK
Eg
gM
DC
KM
DC
KM
DC
K
Fe
rre
t n
um
be
r
Sh
5
39
, 5
40
,
54
3,
54
4,
57
0,
57
1,
57
4*1
,3
F4
1/1
4*2
F2
6/1
3*2
F2
9/1
3*4
F0
1/1
3*4
F0
4/1
3*2
F4
1/1
3*2
F0
9/1
3*2
F1
5/1
6*4
F1
6/1
6*4
Ge
ne
tic
gro
up
1A
1A
1A
1A
1A
1A
1B
1A
1A
RE
FE
RE
NC
E V
IRU
SE
S
B/M
ala
ys
ia/2
50
6/2
00
42
00
4-1
2-0
6E
3/E
71
28
01
60
40
40
80
40
80
10
<<
B/B
ris
ba
ne
/60
/20
08
1A
20
08
-08
-04
E4
/E4
25
60
80
64
03
20
32
01
60
64
08
04
02
0
B/M
alt
a/6
36
71
4/2
01
11
A2
01
1-0
3-0
7E
4/E
12
56
08
06
40
32
03
20
16
06
40
40
40
20
B/J
oh
an
ne
sb
urg
/39
64
/20
12
1A
20
12
-08
-03
E1
/E2
51
20
16
01
28
01
28
01
28
01
28
01
28
01
60
80
80
B/F
orm
os
a/V
23
67
/20
12
1A
20
12
-08
-06
MD
CK
1/M
DC
K3
25
60
20
64
01
60
16
01
60
32
04
02
02
0
B/S
ou
th A
us
tra
lia
/81
/20
12
1A
20
12
-11
-28
E4
/E1
12
80
20
32
01
60
80
80
32
02
0<
10
B/H
on
g K
on
g/5
14
/20
09
1B
20
09
-10
-11
MD
CK
31
28
0<
40
<<
20
20
20
40
20
B/Ire
lan
d/3
15
4/2
01
61
A2
01
6-0
1-1
4M
DC
K1
/MD
CK
42
56
0<
40
<<
40
20
20
40
20
B/N
ord
rhe
in-W
es
tfa
len
/1/2
01
61
A2
01
6-0
1-0
4C
2/M
DC
K1
25
60
10
80
<2
04
04
04
04
04
0
TE
ST
VIR
US
ES
B/R
he
inla
nd
-Pfa
lz/4
3/2
01
6V
ac
cin
e b
rea
kth
rou
gh
1A
20
16
-11
-21
C2
/MD
CK
12
56
04
06
40
<1
60
16
06
40
40
20
20
B/P
ort
ug
al/S
U2
75
/20
17
1A
20
17
-01
-02
MD
CK
12
56
0<
80
<<
40
40
20
40
20
B/A
the
ns
GR
/78
/20
17
1A
20
17
-01
-03
MD
CK
12
56
02
08
0<
20
40
40
20
40
40
*V
ac
cin
e
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
Su
pe
rsc
rip
ts r
efe
r to
an
tis
eru
m p
rop
ert
ies
(<
re
late
s t
o t
he
lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
):
1 <
= <
40
; 2 <
= <
10
; 3 h
yp
eri
mm
un
e s
he
ep
se
rum
; 4 <
= <
20
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
17
Table 5-2. Antigenic analysis of influenza B/Victoria-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Bri
sB
/Ma
lB
/Bri
sB
/Ma
lta
B/J
hb
B/F
or
B/S
th A
us
B/H
KB
/Ire
lan
dB
/No
rd-W
es
t
info
rma
tio
nd
ate
his
tory
60
/08
25
06
/04
60
/08
63
67
14
/11
39
64
/12
V2
36
7/1
28
1/1
25
14
/09
31
54
/16
1/1
6
Pa
ss
ag
e h
isto
ryE
gg
Eg
gE
gg
Eg
gE
gg
MD
CK
Eg
gM
DC
KM
DC
KM
DC
K
Fe
rre
t n
um
be
r
Sh
5
39
, 5
40
,
54
3,
54
4,
57
0,
57
1,
57
4*1
,3
F4
1/1
4*2
F3
7/1
4*2
F2
9/1
3*4
F0
1/1
3*4
F0
4/1
3*2
F4
1/1
3*2
F0
9/1
3*2
F1
5/1
6*2
F1
6/1
6*2
Ge
ne
tic
gro
up
1A
1A
1A
1A
1A
1A
1B
1A
1A
RE
FE
RE
NC
E V
IRU
SE
S
B/M
ala
ys
ia/2
50
6/2
00
42
00
4-1
2-0
6E
3/E
71
28
03
20
40
40
40
40
80
10
<<
B/B
ris
ba
ne
/60
/20
08
1A
20
08
-08
-04
E4
/E4
12
80
80
16
01
60
16
08
03
20
40
20
20
B/M
alt
a/6
36
71
4/2
01
11
A2
01
1-0
3-0
7E
4/E
11
28
08
03
20
32
01
60
16
06
40
40
20
20
B/J
oh
an
ne
sb
urg
/39
64
/20
12
1A
20
12
-08
-03
E1
/E2
51
20
16
06
40
64
06
40
64
06
40
16
08
08
0
B/F
orm
os
a/V
23
67
/20
12
1A
20
12
-08
-06
MD
CK
1/M
DC
K3
25
60
20
16
08
01
60
16
01
60
40
20
10
B/S
ou
th A
us
tra
lia
/81
/20
12
1A
20
12
-11
-28
E4
/E1
12
80
40
16
08
08
08
01
60
20
<1
0
B/H
on
g K
on
g/5
14
/20
09
1B
20
09
-10
-11
MD
CK
31
28
0<
<<
<2
02
02
04
02
0
B/Ire
lan
d/3
15
4/2
01
61
A2
01
6-0
1-1
4M
DC
K1
/MD
CK
42
56
0<
<<
<2
02
02
04
02
0
B/N
ord
rhe
in-W
es
tfa
len
/1/2
01
61
A2
01
6-0
1-0
4C
2/M
DC
K3
25
60
<<
<<
40
40
40
40
40
TE
ST
VIR
US
ES
B/N
ied
ers
ac
hs
en
/4/2
01
71
A2
01
7-0
1-3
0C
1/M
DC
K1
25
60
<<
<<
40
20
20
40
10
B/B
aye
rn/1
0/2
01
71
A2
01
7-0
2-0
2C
1/M
DC
K1
25
60
<<
<<
40
40
20
40
20
B/H
es
se
n/1
/20
17
1A
20
17
-02
-02
C1
/MD
CK
12
56
0<
<<
<4
04
02
04
02
0
B/N
orw
ay/9
98
/20
17
1A
20
17
-02
-08
MD
CK
1/M
DC
K1
25
60
<<
<<
20
40
20
40
20
B/N
orw
ay/1
10
2/2
01
71
A2
01
7-0
2-1
3M
DC
K1
/MD
CK
12
56
0<
<<
<4
04
02
02
02
0
B/N
orw
ay/1
04
0/2
01
71
A2
01
7-0
2-1
5M
DC
K1
/MD
CK
12
56
0<
<<
<4
04
02
04
04
0
B/N
orw
ay/1
07
6/2
01
71
A2
01
7-0
2-1
6M
DC
K1
/MD
CK
15
12
0<
<<
<4
08
04
04
04
0
B/B
ulg
ari
a/5
13
/20
17
1A
20
17
-02
-23
SIA
T2
/MD
CK
11
28
0<
<<
<2
04
02
02
02
0
B/B
ulg
ari
a/5
16
/20
17
1A
20
17
-02
-24
SIA
T2
/MD
CK
12
56
0<
<<
<4
04
02
04
02
0
B/N
ord
rhe
in-W
es
tfa
len
/8/2
01
71
A2
01
7-0
3-0
7C
1/M
DC
K1
25
60
<<
<<
40
40
40
40
20
B/B
rem
en
/4/2
01
71
A2
01
7-0
3-1
3C
1/M
DC
K1
25
60
<<
<<
40
40
20
40
20
*V
ac
cin
e
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
Su
pe
rsc
rip
ts r
efe
r to
an
tis
eru
m p
rop
ert
ies
(<
re
late
s t
o t
he
lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
):
1 <
= <
40
; 2 <
= <
10
; 3 h
yp
eri
mm
un
e s
he
ep
se
rum
; 4 <
= <
20
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
18
Table 5-3. Antigenic analysis of influenza B/Victoria-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Bri
sB
/Ma
lB
/Bri
sB
/Ma
lta
B/J
hb
B/F
or
B/S
th A
us
B/H
KB
/Ire
lan
dB
/No
rd-W
es
t
info
rma
tio
nd
ate
his
tory
60
/08
25
06
/04
60
/08
63
67
14
/11
39
64
/12
V2
36
7/1
28
1/1
25
14
/09
31
54
/16
1/1
6
Pa
ss
ag
e h
isto
ryE
gg
Eg
gE
gg
Eg
gE
gg
MD
CK
Eg
gM
DC
KM
DC
KM
DC
K
Fe
rre
t n
um
be
r
Sh
5
39
, 5
40
,
54
3,
54
4,
57
0,
57
1,
57
4*1
,3
F4
1/1
4*2
NIB
F5
2/1
6*4
F2
9/1
3*4
F0
1/1
3*4
F0
4/1
3*2
F4
1/1
3*2
F0
9/1
3*2
F1
5/1
6*2
F1
6/1
6*2
Ge
ne
tic
gro
up
1A
1A
1A
1A
1A
1A
1B
1A
1A
RE
FE
RE
NC
E V
IRU
SE
S
B/M
ala
ys
ia/2
50
6/2
00
42
00
4-1
2-0
6E
3/E
71
28
03
20
80
40
80
40
80
<<
<
B/B
ris
ba
ne
/60
/20
08
1A
20
08
-08
-04
E4
/E4
25
60
80
64
01
60
16
08
03
20
40
40
20
B/M
alt
a/6
36
71
4/2
01
11
A2
01
1-0
3-0
7E
4/E
12
56
08
06
40
32
01
60
16
03
20
40
40
40
B/J
oh
an
ne
sb
urg
/39
64
/20
12
1A
20
12
-08
-03
E1
/E2
51
20
32
01
28
01
28
01
28
06
40
12
80
16
01
60
16
0
B/F
orm
os
a/V
23
67
/20
12
1A
20
12
-08
-06
MD
CK
1/M
DC
K3
51
20
40
32
08
01
60
16
03
20
40
40
40
B/S
ou
th A
us
tra
lia
/81
/20
12
1A
20
12
-11
-28
E4
/E1
12
80
80
32
08
08
08
03
20
20
20
20
B/H
on
g K
on
g/5
14
/20
09
1B
20
09
-10
-11
MD
CK
32
56
0<
20
20
<2
04
04
08
08
0
B/Ire
lan
d/3
15
4/2
01
61
A2
01
6-0
1-1
4M
DC
K1
/MD
CK
42
56
0<
20
20
<4
04
04
08
08
0
B/N
ord
rhe
in-W
es
tfa
len
/1/2
01
61
A2
01
6-0
1-0
4C
2/M
DC
K3
51
20
<2
02
0<
80
40
40
80
16
0
TE
ST
VIR
US
ES
B/P
ov
azs
ka
Bys
tric
a/1
75
/20
17
1A
20
17
-01
-16
MD
CK
x/M
DC
K1
25
60
<4
01
0<
80
80
20
80
40
B/B
rati
sla
va
/27
5/2
01
71
A2
01
7-0
2-0
1M
DC
Kx
/MD
CK
12
56
0<
40
10
<8
08
02
08
04
0
B/L
atv
ia/0
2-0
45
98
/20
17
1A
20
17
-02
-02
C2
/MD
CK
15
12
0<
20
10
<4
04
04
08
08
0
B/S
as
tin
-Str
aze
/33
2/2
01
71
A2
01
7-0
2-1
3M
DC
Kx
/MD
CK
12
56
0<
40
10
<8
08
02
08
04
0
B/P
op
rad
/32
4/2
01
71
A2
01
7-0
2-1
3M
DC
Kx
/MD
CK
15
12
0<
40
20
<1
60
16
04
08
08
0
B/N
orw
ay/1
16
7/2
01
71
A2
01
7-0
2-1
6M
DC
K2
51
20
<8
02
02
08
08
04
01
60
80
B/L
ith
ua
nia
/62
95
/20
17
1A
20
17
-02
-20
MD
CK
2/M
DC
K1
25
60
20
20
10
<4
04
02
08
08
0
B/S
lov
en
ia/1
49
6/2
01
71
A2
01
7-0
3-2
0M
DC
K1
51
20
<4
02
02
04
08
04
01
60
80
B/L
ith
ua
nia
/10
13
7/2
01
71
A2
01
7-0
3-2
2M
DC
K2
/MD
CK
12
56
0<
20
20
20
40
40
40
80
80
B/N
orw
ay/2
07
7/2
01
72
01
7-0
4-0
1M
DC
K1
/MD
CK
12
56
0<
40
10
<8
08
04
08
04
0
B/K
os
ice
/39
2/2
01
71
A2
01
7-0
4-0
6M
DC
Kx
/MD
CK
15
12
0<
40
10
<8
08
04
08
08
0
B/N
orw
ay/2
21
3/2
01
72
01
7-0
4-1
0M
DC
K1
51
20
<4
02
02
08
08
04
08
08
0
B/S
ac
hs
en
-An
ha
lt/7
/20
17
20
17
-04
-18
C2
/MD
CK
15
12
0<
40
20
20
80
80
40
80
80
B/N
orw
ay/2
30
9/2
01
72
01
7-0
4-2
1M
DC
K1
/MD
CK
12
56
0<
40
10
<4
08
02
08
04
0
B/N
orw
ay/2
30
2/2
01
71
A2
01
7-0
4-2
1M
DC
K1
/MD
CK
12
56
0<
40
20
<8
08
04
08
08
0
B/N
orw
ay/2
42
4/2
01
71
A2
01
7-0
4-2
6M
DC
K1
/MD
CK
12
56
0<
20
20
<8
08
02
08
04
0
B/N
orw
ay/2
40
9/2
01
71
A2
01
7-0
4-2
7M
DC
K1
/MD
CK
18
0<
<<
<<
<<
<<
B/N
orw
ay/2
61
5/2
01
72
01
7-0
4-3
0M
DC
K1
25
60
<4
02
02
08
08
02
08
04
0
*V
ac
cin
e
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
Su
pe
rsc
rip
ts r
efe
r to
an
tis
eru
m p
rop
ert
ies
(<
re
late
s t
o t
he
lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
):
1 <
= <
40
; 2 <
= <
10
; 3 h
yp
eri
mm
un
e s
he
ep
se
rum
; 4 <
= <
20
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
19
Figure 3. Phylogenetic comparison of influenza B/Victoria-lineage HA genes
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
20
Table 6-1. Antigenic analysis of influenza B/Yamagata-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Ph
uk
et
B/F
lB
/Bri
sB
/Es
ton
iaB
/Ma
ss
B/M
as
sB
/Wis
B/S
toc
kB
/Ph
uk
et
B/P
hu
ke
tB
/HK
info
rma
tio
nd
ate
his
tory
30
73
/13
4/0
63
/07
55
66
9/1
10
2/1
20
2/1
21
/10
12
/11
30
73
/13
30
73
/13
34
17
/14
Pa
ss
ag
e h
isto
ryE
gg
Eg
gE
gg
MD
CK
MD
CK
Eg
gE
gg
Eg
gM
DC
KE
gg
Eg
g
Fe
rre
t n
um
be
rS
H6
14
*1,3
F1
7/1
3*1
F3
8/1
4*2
F2
7/1
3*1
F0
5/1
5*1
F4
2/1
4*2
F1
0/1
3*2
F0
6/1
5*2
F3
5/1
4*2
F3
7/1
4*2
St
Ju
de
s
F7
15
/14
*1,4
Ge
ne
tic
Gro
up
31
22
22
33
33
3
RE
FE
RE
NC
E V
IRU
SE
S
B/F
lori
da
/4/2
00
61
20
06
-12
-15
E7
/E1
25
60
64
06
40
32
01
60
64
01
60
16
02
01
60
16
0
B/B
ris
ba
ne
/3/2
00
72
20
07
-09
-03
E2
/E2
25
60
12
80
12
80
32
01
60
12
80
32
03
20
20
32
03
20
B/E
sto
nia
/55
66
9/2
01
12
20
11
-03
-14
MD
CK
2/M
DC
K3
12
80
80
80
64
01
60
40
40
20
40
40
16
0
B/M
as
sa
ch
us
ett
s/0
2/2
01
22
20
12
-03
-13
MD
CK
1/C
2/M
DC
K3
12
80
32
03
20
64
03
20
32
01
60
80
40
16
03
20
B/M
as
sa
ch
us
ett
s/0
2/2
01
22
20
12
-03
-13
E3
/E3
64
03
20
32
01
60
80
32
04
08
0<
80
16
0
B/W
isc
on
sin
/1/2
01
03
20
10
-02
-20
E3
/E2
51
20
64
03
20
32
04
06
40
64
03
20
80
64
06
40
B/S
toc
kh
olm
/12
/20
11
32
01
1-0
3-2
8E
x/E
21
28
01
60
80
40
<8
08
01
60
20
80
80
B/P
hu
ke
t/3
07
3/2
01
33
20
13
-11
-21
MD
CK
2/M
DC
K2
51
20
32
03
20
32
06
40
32
03
20
16
06
40
32
03
20
B/P
hu
ke
t/3
07
3/2
01
33
20
13
-11
-21
E4
/E3
25
60
16
01
60
40
10
16
01
60
80
20
16
01
60
B/H
on
g K
on
g/3
41
7/2
01
43
20
14
-06
-04
E4
/E1
12
80
80
40
40
10
80
80
40
10
80
16
0
TE
ST
VIR
US
ES
A/D
en
ma
rk/4
8/2
01
63
20
16
-10
-06
SIA
T2
/MD
CK
1/S
IAT
12
56
08
01
60
80
80
80
16
04
08
08
01
60
B/S
ac
hs
en
/74
/20
16
32
01
6-1
1-2
1C
1/M
DC
K1
12
80
40
20
80
40
20
40
20
80
40
16
0
B/L
ux
em
bo
urg
/63
55
0/2
01
63
20
16
-12
-15
MD
CK
11
28
04
02
04
02
02
04
02
04
04
08
0
B/C
ata
lon
ia/2
13
42
58
NS
/20
17
32
01
7-0
1-0
4C
0/M
DC
K1
25
60
16
01
60
80
32
01
60
16
04
01
60
16
01
60
B/N
orw
ay/8
77
/20
17
32
01
7-0
1-2
5M
DC
K1
/MD
CK
11
28
04
04
04
02
04
04
02
04
04
08
0
B/R
he
inla
nd
-Pfa
lz/1
/20
17
32
01
7-0
1-3
1C
1/M
DC
K1
12
80
40
80
40
20
40
80
20
40
40
80
*S
up
ers
cri
pts
re
fer
to a
nti
se
rum
pro
pe
rtie
s (
< r
ela
tes
to
th
e lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
):V
ac
cin
e#
1 <
= <
40
; 2
< =
<1
0;
3 h
yp
eri
mm
un
e s
he
ep
se
rum
; 4
RD
E s
eru
m p
re-a
ds
orb
ed
wit
h T
RB
C
#B
/Ya
ma
ga
ta-l
ine
ag
e v
iru
s r
ec
om
me
nd
ed
fo
r u
se
in
qu
ad
riv
ale
nt
va
cc
ine
s
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
21
Table 6-2. Antigenic analysis of influenza B/Yamagata-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Ph
uk
et
B/F
lB
/Bri
sB
/Es
ton
iaB
/Ma
ss
B/M
as
sB
/Wis
B/S
toc
kB
/Ph
uk
et
B/P
hu
ke
tB
/HK
info
rma
tio
nd
ate
his
tory
30
73
/13
4/0
63
/07
55
66
9/1
10
2/1
20
2/1
21
/10
12
/11
30
73
/13
30
73
/13
34
17
/14
Pa
ss
ag
e h
isto
ryE
gg
Eg
gE
gg
MD
CK
MD
CK
Eg
gE
gg
Eg
gM
DC
KE
gg
Eg
g
Fe
rre
t n
um
be
rS
H6
14
*1,3
F1
7/1
3*1
F3
8/1
4*2
F2
7/1
3*5
F0
5/1
5*2
F4
2/1
4*2
F1
0/1
3*2
F0
6/1
5*2
F3
5/1
4*2
NIB
F5
1/1
6*2
St
Ju
de
s
F7
15
/14
*2,4
Ge
ne
tic
Gro
up
31
22
22
33
33
3
RE
FE
RE
NC
E V
IRU
SE
S
B/F
lori
da
/4/2
00
61
20
06
-12
-15
E7
/E1
12
80
64
06
40
16
08
06
40
16
01
60
10
16
01
60
B/B
ris
ba
ne
/3/2
00
72
20
07
-09
-03
E2
/E2
12
80
64
06
40
16
01
60
64
01
60
16
0<
32
01
60
B/E
sto
nia
/55
66
9/2
01
12
20
11
-03
-14
MD
CK
2/M
DC
K3
64
04
04
03
20
16
02
01
0<
<4
08
0
B/M
as
sa
ch
us
ett
s/0
2/2
01
22
20
12
-03
-13
MD
CK
1/C
2/M
DC
K3
12
80
32
03
20
32
01
60
32
08
08
01
08
01
60
B/M
as
sa
ch
us
ett
s/0
2/2
01
22
20
12
-03
-13
E3
/E3
12
80
32
06
40
16
08
06
40
80
80
<3
20
16
0
B/W
isc
on
sin
/1/2
01
03
20
10
-02
-20
E3
/E2
25
60
32
03
20
80
<3
20
32
01
60
40
32
01
60
B/S
toc
kh
olm
/12
/20
11
32
01
1-0
3-2
8E
4/E
11
28
08
08
0<
<8
04
08
0<
40
80
B/P
hu
ke
t/3
07
3/2
01
33
20
13
-11
-21
MD
CK
2/M
DC
K2
51
20
16
03
20
16
03
20
32
03
20
80
32
03
20
16
0
B/P
hu
ke
t/3
07
3/2
01
33
20
13
-11
-21
E4
/E3
25
60
32
01
60
40
10
16
01
60
80
20
32
01
60
B/H
on
g K
on
g/3
41
7/2
01
43
20
14
-06
-04
E4
/E1
12
80
40
40
<<
40
40
20
<4
01
60
TE
ST
VIR
US
ES
B/S
lov
en
ia/7
41
/20
17
32
01
7-0
1-3
0M
DC
Kx
/MD
CK
12
56
08
01
60
80
80
80
16
04
08
08
01
60
B/S
lov
en
ia/7
39
/20
17
32
01
7-0
1-3
0M
DC
K1
/MD
CK
15
12
03
20
32
01
60
16
03
20
16
08
03
20
16
03
20
B/S
lov
en
ia/8
16
/20
17
32
01
7-0
2-0
1M
DC
Kx
/MD
CK
15
12
01
60
16
01
60
80
16
01
60
40
16
01
60
16
0
B/N
ied
ers
ac
hs
en
/3/2
01
73
20
17
-02
-06
C1
/MD
CK
11
28
04
04
04
02
04
08
02
04
04
08
0
B/Ic
ela
nd
/09
/20
17
32
01
7-0
2-0
7M
DC
K1
/MD
CK
11
28
08
08
08
04
08
08
02
08
04
08
0
B/L
atv
ia/0
2-0
18
88
5/2
01
7
32
01
7-0
2-0
7C
2/M
DC
K1
51
20
32
03
20
32
06
40
32
03
20
16
06
40
32
03
20
B/N
orw
ay/1
07
3/2
01
73
20
17
-02
-13
MD
CK
1/M
DC
K1
25
60
40
80
80
40
80
80
20
80
40
16
0
B/L
atv
ia/0
2-0
31
65
4/2
01
7
32
01
7-0
2-1
3C
2/M
DC
K1
25
60
80
16
01
60
16
01
60
16
04
01
60
80
32
0
B/N
orw
ay/1
01
4/2
01
73
20
17
-02
-14
MD
CK
1/M
DC
K1
25
60
40
40
80
40
40
80
20
40
40
80
B/N
ord
rhe
in-W
es
tfa
len
/5/2
01
73
20
17
-02
-14
C1
/MD
CK
11
28
08
08
04
02
04
08
02
04
04
01
60
B/N
orw
ay/1
15
2/2
01
73
20
17
-02
-15
MD
CK
1/M
DC
K1
25
60
40
80
80
40
80
80
20
40
40
16
0
B/B
rem
en
/2/2
01
73
20
17
-02
-15
C1
/MD
CK
11
28
04
04
04
02
04
04
02
04
04
08
0
B/L
atv
ia/0
2-0
58
11
3/2
01
73
20
17
-02
-21
C2
/MD
CK
12
56
08
08
08
08
08
08
02
08
08
01
60
B/Ic
ela
nd
/46
/20
17
32
01
7-0
2-2
4M
DC
K1
/MD
CK
12
56
01
60
16
01
60
32
01
60
16
08
06
40
16
01
60
B/Ic
ela
nd
/45
/20
17
32
01
7-0
2-2
4M
DC
K1
/MD
CK
11
28
04
08
04
02
08
08
02
04
08
08
0
B/N
orw
ay/1
47
3/2
01
73
20
17
-02
-25
MD
CK
25
12
01
60
16
08
08
01
60
16
04
01
60
16
01
60
B/S
lov
en
ia/1
32
1/2
01
73
20
17
-02
-27
MD
CK
1/M
DC
K1
51
20
80
16
08
08
01
60
16
04
01
60
80
32
0
B/N
orw
ay/1
48
4/2
01
73
20
17
-02
-28
MD
CK
15
12
08
08
08
08
08
01
60
40
80
80
16
0
B/Ic
ela
nd
/58
/20
17
32
01
7-0
3-0
3M
DC
K1
/MD
CK
11
28
04
08
08
04
08
04
02
04
04
08
0
B/N
orw
ay/1
47
1/2
01
73
20
17
-03
-03
MD
CK
12
56
08
08
08
08
04
08
04
08
08
01
60
B/Ic
ela
nd
/62
/20
17
32
01
7-0
3-0
6M
DC
Kx
/MD
CK
12
56
01
60
16
03
20
64
03
20
16
08
06
40
32
01
60
B/L
ith
ua
nia
/86
22
/20
17
32
01
7-0
3-1
0M
DC
K2
/MD
CK
15
12
01
60
16
01
60
32
03
20
16
08
01
60
16
01
60
B/L
ith
ua
nia
/88
65
/20
17
32
01
7-0
3-1
4M
DC
K2
/MD
CK
12
56
04
08
08
04
04
08
02
04
04
01
60
B/S
lov
en
ia/1
42
7/2
01
73
20
17
-03
-14
MD
CK
1/M
DC
K1
25
60
80
80
80
40
40
80
20
40
80
16
0
B/S
lov
en
ia/1
45
8/2
01
72
01
7-0
3-1
6S
IAT
x/M
DC
K1
51
20
16
01
60
16
01
60
16
01
60
40
16
01
60
32
0
B/S
lov
en
ia/1
46
7/2
01
73
20
17
-03
-20
SIA
Tx
/MD
CK
12
56
04
08
08
04
04
08
02
08
04
01
60
B/L
ith
ua
nia
/94
64
/20
17
32
01
7-0
3-2
0M
DC
K2
/MD
CK
15
12
03
20
32
06
40
12
80
32
03
20
16
01
28
03
20
32
0
B/L
ith
ua
nia
/10
11
5/2
01
73
20
17
-03
-23
MD
CK
2/M
DC
K1
25
60
80
80
80
40
80
80
40
80
80
16
0
B/S
lov
en
ia/1
56
0/2
01
73
20
17
-03
-27
MD
CK
x/M
DC
K1
25
60
40
80
40
40
40
80
20
40
40
16
0
B/L
atv
ia/0
3-0
82
70
8/2
01
73
20
17
-03
-30
C2
/MD
CK
12
56
08
08
01
60
16
08
08
04
01
60
80
16
0
B/L
atv
ia/0
4-0
14
58
5/2
01
73
20
17
-04
-05
C1
/MD
CK
11
28
04
08
04
08
04
04
02
04
04
01
60
B/S
lov
en
ia/1
66
6/2
01
73
20
17
-04
-11
MD
CK
x/M
DC
K1
25
60
40
80
80
40
40
80
20
40
40
16
0
*S
up
ers
cri
pts
re
fer
to a
nti
se
rum
pro
pe
rtie
s (
< r
ela
tes
to
th
e lo
we
st
dilu
tio
n o
f a
nti
se
rum
us
ed
):V
ac
cin
e#
1 <
= <
40
; 2
< =
<1
0;
3 h
yp
eri
mm
un
e s
he
ep
se
rum
; 4
RD
E s
eru
m p
re-a
ds
orb
ed
wit
h T
RB
C;
5 <
= <
20
#B
/Ya
ma
ga
ta-l
ine
ag
e v
iru
s r
ec
om
me
nd
ed
fo
r u
se
in
qu
ad
riv
ale
nt
va
cc
ine
s
Se
qu
en
ce
s in
ph
ylo
ge
ne
tic
tre
es
Ha
em
ag
glu
tin
ati
on
in
hib
itio
n t
itre
Po
st-
infe
cti
on
fe
rre
t a
nti
se
ra
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
22
Table 6-3. Antigenic analysis of influenza B/Yamagata-lineage viruses by HI
Vir
us
es
Oth
er
Co
lle
cti
on
Pa
ss
ag
eB
/Ph
uk
et
B/F
lB
/Bri
sB
/Es
ton
iaB
/Ma
ss
B/M
as
sB
/Wis
B/S
toc
kB
/Ph
uk
et
B/P
hu
ke
tB
/HK
info
rma
tio
nd
ate
his
tory
30
73
/13
4/0
63
/07
55
66
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ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
23
Figure 4. Phylogenetic comparison of influenza B/Yamagata-lineage HA genes
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
24
Summary of genetic data submitted to TESSy For the 2016–2017 season beginning week 40/2016 until week 31/2017, 4483 viruses have been characterised genetically: 17 were defined as A(H1N1)pdm09 clade 6B represented by A/South Africa/3626/2013 and 55 were subclade 6B.1 as represented by A/Michigan/45/2015; 1178 were A(H3N2) subclade 3C.2a represented by A/Hong Kong/4801/2014, 2653 subclade 3C.2a1 represented by A/Bolzano/7/2016, 43 were subclade 3C.3a represented by A/Switzerland/9715293/2013, one was subclade 3C.3 represented by A/Samara/73/2013, and five belonged to a group that was unlisted; 171 were B/Victoria-lineage clade 1A represented by B/Brisbane/60/2008 and one clade 1B was represented by B/Hong Kong/514/2009; 346 were B/Yamagata-lineage clade 3 represented by B/Phuket/3073/2013, with 13 unattributed.
Antiviral susceptibility Phenotypic testing for susceptibility to oseltamivir and zanamivir has been conducted on 800 viruses at the WIC:
35 A(H1N1)pdm09, 652 A(H3N2), 38 B/Victoria-lineage and 75 B/Yamagata-lineage viruses. All A(H1N1)pdm09 and B viruses showed normal inhibition (NI) by these neuraminidase inhibitors. Four A(H3N2) viruses showed reduced inhibition with oseltamivir: A/Poland/30484/2016, A/Poland/17C/2017, A/Poland/12186/2016, and A/Luxembourg/61798/2016, the latter two also showing reduced inhibition with zanamivir.
For weeks 40/2016–26/2017 of the 2016–2017 influenza season, countries reported on the antiviral susceptibility of 61 A(H1N1)pdm09 viruses, 3086 A(H3N2) viruses and 325 influenza type B viruses from sentinel and non-sentinel sources to TESSy. All but four showed no molecular or phenotypic evidence of reduced inhibition by neuraminidase inhibitors (oseltamivir and zanamivir); three A(H3N2) isolates showed reduced inhibition by both oseltamivir and zanamivir, and one B isolate gave reduced inhibition with oseltamivir only.
Influenza A(H7N9) virus On 1 April 2013, the World Health Organization (WHO) Global Alert and Response [3] reported that the China Health and Family Planning Commission notified the WHO of three cases of human infection with influenza A(H7N9). A description of the characteristics of H7N9 viruses can be found on the WHO website [4]. Increased numbers of cases have been reported over the course of the following seasons and cases have been reported in 2017 [5]. A revised Rapid Risk Assessment [6] for these A(H7N9) viruses was carried out by ECDC and posted on 11 February 2015 and most recently updated on 3 July 2017 [7]. WHO posted an analysis of recent information on A(H7N9) viruses on 10 February 2017 [8] and a summary and assessment of influenza viruses at the human-animal interface on 15 June 2017 [9], with the latest cases being reported on 19 July 2017 [10].
Influenza A(H5) virus The most recent monthly risk assessment of influenza at the human-animal interface was published by WHO on 15 June 2017 [9]. ECDC published an updated rapid risk assessment on the situation in Egypt on 13 March 2015 [11] and an epidemiological update on 10 April 2015 [12]. On 18 November 2016, ECDC published a rapid risk assessment related to outbreaks of highly pathogenic avian influenza H5N8 viruses in Europe [13].
WHO CC reports A description of results generated by the WHO Collaborating Centre for Reference and Research on Influenza at the Crick Worldwide Influenza Centre (Francis Crick Institute) and used at the WHO vaccine composition meetings held at WHO Geneva 26–28 September 2016 and 27 February–1 March 2017 can be found at:
https://www.crick.ac.uk/media/326439/september_2016_interim_report.pdf and
https://www.crick.ac.uk/media/358671/crick_nh_vcm_report_feb_2017_v2.pdf
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
25
Note on the figures The phylogenetic trees were constructed using RAxML, drawn using FigTree and annotated using Adobe Illustrator. The bars indicate the proportion of nucleotide changes between sequences. Reference strains are viruses to which post-infection ferret antisera have been raised. The colours indicate the month of sample collection. Isolates from WHO NICs in EU/EEA countries are marked (#). Sequences for some viruses from non-EU/EEA countries were recovered from GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu database which were downloaded for use in the preparation of this report (all submitters of data may be contacted directly via the GISAID website), along with all laboratories who submitted sequences directly to the London WHO Collaborating Centre.
ECDC SURVEILLANCE REPORT Influenza virus characterisation, June 2017
26
References 1. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2017
southern hemisphere influenza season. Wkly Epidemiol Rec. 2016 Oct 14;91(41):469-84. Available from: http://apps.who.int/iris/bitstream/10665/250513/1/WER9141.pdf
2. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season. Wkly Epidemiol Rec. 2017 Mar 17;92(11):117-28. http://apps.who.int/iris/bitstream/10665/254756/1/WER9211.pdf.
3. World Health Organization. Emergencies preparedness, response – Human infection with influenza A(H7N9) virus in China. 1 April 2013 [internet]. Geneva: WHO; 2013 [accessed 21 Aug 2017]. Available from: http://www.who.int/csr/don/2013_04_01/en/index.html
4. World Health Organization. Influenza – Avian influenza A(H7N9) virus [internet]. Geneva: WHO; 2017 [accessed 21 Aug 2017]. Available from:
http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/
5. World Health Organization. Emergencies preparedness, response –Human infection with avian influenza A(H7N9) virus – China [internet]. Geneva: WHO; 2017 [accessed 21 Aug 2017]. Available from: http://www.who.int/csr/don/19-july-2017-ah7n9-china/en/
6. European Centre for Disease Prevention and Control. Human infection by low pathogenic avian influenza A(H7) viruses – 11 February 2015. Stockholm: ECDC; 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/RRA-Influenza-A-H7.pdf
7. European Centre for Disease Prevention and Control. Influenza A(H7N9) virus in China – Implications for public health – Seventh update, 3 July 2017. Stockholm: ECDC; 2017. Available from: https://ecdc.europa.eu/sites/portal/files/documents/2017-07-03-RRA-Disease-China_H7N9_0.pdf
8. World Health Organization. Analysis of recent scientific information on avian influenza A(H7N9) virus. 10 February 2017 [internet]. Geneva: WHO, 2017 [accessed 21 Aug 2017]. Available from:
http://www.who.int/influenza/human_animal_interface/avian_influenza/riskassessment_AH7N9_201702/en
9. World Health Organization. Influenza at the human-animal interface. Summary and assessment as of 15 June 2017. Geneva: WHO; 2017. Available from: http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_06_15_2017.pdf
10. World Health Organization. Emergencies preparedness, response – Human infection with avian influenza A(H7N9) virus – China. 19 July 2017 [internet]. Geneva: WHO; 2017 [accessed 21 Aug 2017]. Available from: http://www.who.int/csr/don/19-july-2017-ah7n9-china/en/
11. European Centre for Disease Prevention and Control. Human infection with avian influenza A(H5N1) virus, Egypt – first update. 13 March 2015. Stockholm: ECDC; 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/Rapid-Risk-Assessment-Influenza-A-H5N1-Egypt-March-2015.pdf
12. European Centre for Disease Prevention and Control. Epidemiological update: increase in reporting of human cases of A(H5N1) influenza, Egypt [internet]. Stockholm: ECDC; 2015. Available from: http://ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?List=8db7286c-fe2d-476c-9133-18ff4cb1b568&ID=1199
13. European Centre for Disease Prevention and Control. Outbreak of highly pathogenic avian influenza A(H5N8) in Europe – 18 November 2016. Stockholm: ECDC; 2016. Available from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/risk-assessment-avian-influenza-H5N8-europe.pdf
14. The Francis Crick Institute. Report prepared for the WHO annual consultation on the composition of influenza vaccine for the northern hemisphere 2017–2018, 27 February – 1 March 2017. London: Francis Crick Institute; 2017. Available from: https://www.crick.ac.uk/media/358671/crick_nh_vcm_report_feb_2017_v2.pdf